藤平 篤志

In the present study, we have examined whether the effects: of dexamethasone on follicle stimulating hormone (FSH) secretion were mediated by hypophysiotropic factors, and whether the increased levels of FSH induced by dexamethasone can stimulate ovarian functions in equine chorionic gonadotropin (eCG)-primed immature female rats. Dexamethasone (500 mug) significantly increased serum concentrations of FSH in hypophysectomized rats implanted with pituitary under the kidney capsule, as well as in intact rats. Serum concentrations of inhibin and estradiol in eCG (2.5, 5 i.u.)-primed rats were significantly increased by simultaneous treatment with dexamethasone (500 mug) and eCG, These simultaneous effects were not confirmed in hypophysectomized rats. The results had shown that hypophysiotropic factors do not mediate the selective increase of FSH secretion caused by dexamethasone. Dexamethasone induces the excess amount of FSH secretion from anterior pituitary and this FSH can stimulate inhibin and estradiol secretion in eCG-primed immature female rat. (C) 2001 Elsevier Science Inc. All rights reserved.

Effects of a xenobiotic estrogen, bisphenol A (BPA), on reproductive functions were investigated using adult male rats. BPA was dissolved into sesame oil and injected sc every day (1 mg/rat) for 14 days. Animals were killed by decapitation after the final administration of BPA, and the trunk blood, pituitary, and testes were collected. Plasma concentrations of prolactin were dramatically increased and pituitary contents of prolactin were slightly increased in the BPA group compared to the control group. Plasma concentrations of testosterone were decreased and plasma concentrations of LH were increased in BPA-treated rats compared to control rats. Testicular contents of inhibin were decreased in BPA-treated rats compared to control rats, although plasma concentrations of inhibin were not changed after administration of BPA. The testicular response to hCG for progesterone and testosterone release was decreased in BPA-treated rats. Administration of BPA did not change the pituitary response to luteinizing hormone-releasing hormone (LH-RH) in castrated male rats treated with testosterone. Male sexual behavior also was not changed as a result of BPA treatment. These results suggest that BPA directly inhibits testicular functions and the increased level of plasma LH is probably due to a reduction in the negative feedback regulation by testosterone. The testis is probably a more sensitive site for BPA action than the hypothalamus-pituitary axis.

To elucidate the effects of ultrasound-guided transvaginal follicular aspiration, plasma concentrations of FSH, LH, inhibin, estradiol-17 beta and progesterone, and folliculogenesis were examined in Holstein cows. Four clinically healthy cows with regular estrous cycles were scanned by ultrasound per rectum once a week for 9 weeks before the commencement of follicular aspiration. All visible follicles were divided into 3 categories based on their sizes (2 less than or equal to small < 5 mm; 5 <less than or equal to> medium < 10 mm, large <greater than or equal to> 10 mm). The follicular aspiration was started at random during the estrous cycle and conducted under epidural anesthesia induced with 5 ml of 2% lidocaine once a week for 6 weeks. The average number of total visible follicles greater than or equal to 2 mm in diameter at 7 days after aspiration (21.7 +/- 7.4, n=24) was similar to that before starting aspiration (26.7 +/- 10.5, n=36). Plasma inhibin and estradiol-17 beta declined and fell to a trough on 1.5 days and returned to pre-aspiration values by 5 days after aspiration. Plasma concentrations of FSH increased and reached peak levels between 1 and 1.5 days after aspirations. Plasma concentrations of LH also increased and reached peak levels between 0.5 and 1.5 days after aspirations. Both plasma FSH and LH had returned to pre-aspiration levels by 5 days after aspirations. Plasma concentrations of progesterone did not change with the follicular aspiration. These results demonstrate that follicular aspiration decreases plasma concentrations of inhibin and estradiol-17 beta, which in turn leads to a rise in plasma concentrations of FSH and LH. It is suggested that marked increases in plasma concentrations of FSH and LH after the aspiration stimulate the development and maturation of a new cohort of follicles within one week in cows.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a relatively new neu ro peptide, a nd it has a potent stimulatory effect on adenylate cyclase activity in rat pituitary cells. However, the role of PACAP in the physio logical control of prolactin (PRL) secretion is still unclear. in the present study, we investigated the physiological significance of endogenous PACAP on PRL secretion in lactating rats. On lactation days 7-8, pups were sepa rated from their mother rats for 5 h before the onset of suckling and PACAPs(6-38) (16 mug), a receptor antagonist, was injected through the lateral ventricle cannula just after the removal of pups. The effects of PACAP(6-38) On PRL and oxytocin secretion, and on the activity of tyrosine hydroxylase (TH), were examined after the onset of suckling. Administration of PACAP(6-38) inhibited PRL levels in response to suckling, but it did not affect the activity of TH, as measured by DOPA accumulation at 15 min after administration of NSD 1015 (25.0 mg/kg), an L-aromatic amino acid decarboxylase inhibitor, or the plasma concentrations of oxytocin in lactating rats. injection of alpha -methyl-p-tyrosine (alpha -MT; 50 mg/kg), an inhibitor of dopamine synthesis, increased PRL levels, and suckling caused a further increase in the plasma concentrations of PRL. An injection of PACAP(6-38) (i.c.v.) also inhibited the PRL response to suckling under dopamine depletion. These results suggest that endogenous PACAP acts as a neurotransmitter or neuromodulator within the hypothalamus and plays an important role for PRL secretion in lactating rats. Endogenous PACAP may regulate PRL secretion, possibly mediated by PRL-releasing factors such as vasoactive intestinal polypeptide or vasopressin. Copyright (C) 2001 S. Karger AG, Basel.

Corticotropin releasing-hormone (CRH) is recognized as modulating luteinizing hormone releasing hormone (LH-RH) secretion at the medial preoptic area (MPOA), but the physiological significance of the effects of endogenous CRH on LH-RH secretion at the median eminence (ME) is not clear. To clarify the effects of CRH at ME, we used two animal models (adrenalectomized and restraint stressed rats) for hypersecretion of CRH and examined the effects of iv administration of CRH antiserum on LH secretion. Adrenalectomy for 2 weeks clearly increased plasma concentrations of ACTH and decreased plasma concentrations of LH in adult male rats. The iv injection of CRH antiserum attenuated the increased levels of plasma ACTH and restored the suppressed levels of plasma LH in adrenalectomized rats. In response to restraint stress, plasma concentrations of ACTH and PRL were increased and plasma concentrations of LH were decreased in adult male rats. The iv injection of CRH antiserum blocked the suppression of LH secretion induced by stress, but it did not have any effects on PRL secretion. These results suggest that immunoneutralization of endogenous CRH at the ME increases LH secretion probably mediated by LH-RH release and ME is probably one of the action sites of CRH on LH-RH secretion in addition to MPOA.

Corticotropin releasing-hormone (CRH) is recognized as modulating luteinizing hormone releasing hormone (LH-RH) secretion at the medial preoptic area (MPOA), but the physiological significance of the effects of endogenous CRH on LH-RH secretion at the median eminence (ME) is not clear. To clarify the effects of CRH at ME, we used two animal models (adrenalectomized and restraint stressed rats) for hypersecretion of CRH and examined the effects of iv administration of CRH antiserum on LH secretion. Adrenalectomy for 2 weeks clearly increased plasma concentrations of ACTH and decreased plasma concentrations of LH in adult male rats. The iv injection of CRH antiserum attenuated the increased levels of plasma ACTH and restored the suppressed levels of plasma LH in adrenalectomized rats. In response to restraint stress, plasma concentrations of ACTH and PRL were increased and plasma concentrations of LH were decreased in adult male rats. The iv injection of CRH antiserum blocked the suppression of LH secretion induced by stress, but it did not have any effects on PRL secretion. These results suggest that immunoneutralization of endogenous CRH at the ME increases LH secretion probably mediated by LH-RH release and ME is probably one of the action sites of CRH on LH-RH secretion in addition to MPOA.

To elucidate the effects of ultrasound-guided transvaginal follicular aspiration, plasma concentrations of FSH, LH, inhibin, estradiol-17 beta and progesterone, and folliculogenesis were examined in Holstein cows. Four clinically healthy cows with regular estrous cycles were scanned by ultrasound per rectum once a week for 9 weeks before the commencement of follicular aspiration. All visible follicles were divided into 3 categories based on their sizes (2 less than or equal to small < 5 mm; 5 <less than or equal to> medium < 10 mm, large <greater than or equal to> 10 mm). The follicular aspiration was started at random during the estrous cycle and conducted under epidural anesthesia induced with 5 ml of 2% lidocaine once a week for 6 weeks. The average number of total visible follicles greater than or equal to 2 mm in diameter at 7 days after aspiration (21.7 +/- 7.4, n=24) was similar to that before starting aspiration (26.7 +/- 10.5, n=36). Plasma inhibin and estradiol-17 beta declined and fell to a trough on 1.5 days and returned to pre-aspiration values by 5 days after aspiration. Plasma concentrations of FSH increased and reached peak levels between 1 and 1.5 days after aspirations. Plasma concentrations of LH also increased and reached peak levels between 0.5 and 1.5 days after aspirations. Both plasma FSH and LH had returned to pre-aspiration levels by 5 days after aspirations. Plasma concentrations of progesterone did not change with the follicular aspiration. These results demonstrate that follicular aspiration decreases plasma concentrations of inhibin and estradiol-17 beta, which in turn leads to a rise in plasma concentrations of FSH and LH. It is suggested that marked increases in plasma concentrations of FSH and LH after the aspiration stimulate the development and maturation of a new cohort of follicles within one week in cows.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a relatively new neu ro peptide, a nd it has a potent stimulatory effect on adenylate cyclase activity in rat pituitary cells. However, the role of PACAP in the physio logical control of prolactin (PRL) secretion is still unclear. in the present study, we investigated the physiological significance of endogenous PACAP on PRL secretion in lactating rats. On lactation days 7-8, pups were sepa rated from their mother rats for 5 h before the onset of suckling and PACAPs(6-38) (16 mug), a receptor antagonist, was injected through the lateral ventricle cannula just after the removal of pups. The effects of PACAP(6-38) On PRL and oxytocin secretion, and on the activity of tyrosine hydroxylase (TH), were examined after the onset of suckling. Administration of PACAP(6-38) inhibited PRL levels in response to suckling, but it did not affect the activity of TH, as measured by DOPA accumulation at 15 min after administration of NSD 1015 (25.0 mg/kg), an L-aromatic amino acid decarboxylase inhibitor, or the plasma concentrations of oxytocin in lactating rats. injection of alpha -methyl-p-tyrosine (alpha -MT; 50 mg/kg), an inhibitor of dopamine synthesis, increased PRL levels, and suckling caused a further increase in the plasma concentrations of PRL. An injection of PACAP(6-38) (i.c.v.) also inhibited the PRL response to suckling under dopamine depletion. These results suggest that endogenous PACAP acts as a neurotransmitter or neuromodulator within the hypothalamus and plays an important role for PRL secretion in lactating rats. Endogenous PACAP may regulate PRL secretion, possibly mediated by PRL-releasing factors such as vasoactive intestinal polypeptide or vasopressin. Copyright (C) 2001 S. Karger AG, Basel.

To elucidate the influence of interleukin-6 (IL-6) on the maturation of rat granulosa cell (GC), we have established a differentiation model of rat GC in vitro and examined the expression of IL-6 and its receptors, and its possible actions during GC maturation. Bioactive IL-6 was detectable in the conditioned media of GC at similar to 2.5 ng/ml/24 h per 5 x 10(5) cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that messenger RNAs encoding components of functional IL-6 receptor, namely both ligand-binding subunit (IL-6R) and gp130, were expressed in GC. Treatment of GC with IL-6 for 72 h during the process of in vitro GC maturation dose-dependently inhibited the accumulation of estradiol-17 beta (E-2) and the expression of cytochrome P450 aromatase (P450arom). IL-6 did not change nitric oxide (NO) production and inducible NO synthase expression, implying that IL-6-induced suppression on E-2 levels is dissociated with NO expression. Further, GC which had been incubated with neutralizing anti-IL-6 antibody showed a distinct increase in the levels of P450arom mRNA. These results suggest that IL-6 may attenuate E-2 production partially by inhibiting the expression of aromatase mRNA as an intraovarian regulator for suppressing GC maturation. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

We have previously reported that dexamethasone increased follicle-stimulating hormone (FSH) secretion via suppression of inhibin in immature female rats. In the present study, we investigated the effects of dexamethasone or triamcinolone on follicular development and ovarian functions (estradiol and inhibin secretion) in equine chorionic gonadotropin (eCG)-primed immature female rats. Dexamethasone significantly increased the number of ovulated oocytes in immature female rats treated with 5 i.u. eCG. Serum concentration of FSH in eCG-treated female rats was increased by administration of dexamethasone or triamcinolone, showing the peak value at 9 h after its administration, although the levels of inhibin markedly decreased at that time. Serum concentrations of inhibin and estradiol in eCG-treated female rats increased at 24 h after administration of dexamethasone or triamcinolone. These results demonstrate that dexamethasone or triamcinolone increases FSH secretion, and the excess amount of FSH strongly stimulates follicular development cooperating with exogenous eCG.

We have previously reported that dexamethasone increased follicle-stimulating hormone (FSH) secretion via suppression of inhibin in immature female rats. In the present study, we investigated the effects of dexamethasone or triamcinolone on follicular development and ovarian functions (estradiol and inhibin secretion) in equine chorionic gonadotropin (eCG)-primed immature female rats. Dexamethasone significantly increased the number of ovulated oocytes in immature female rats treated with 5 i.u. eCG. Serum concentration of FSH in eCG-treated female rats was increased by administration of dexamethasone or triamcinolone, showing the peak value at 9 h after its administration, although the levels of inhibin markedly decreased at that time. Serum concentrations of inhibin and estradiol in eCG-treated female rats increased at 24 h after administration of dexamethasone or triamcinolone. These results demonstrate that dexamethasone or triamcinolone increases FSH secretion, and the excess amount of FSH strongly stimulates follicular development cooperating with exogenous eCG.

In order to understand the mechanism by which thyroid hormones alter prolactin (PRL) secretion, we investigated the role of tuberoinfundibular dopamine (TIDA) neurons and pituitary and hypothalamus vasoactive intestinal peptide (VIP) in thiouracil- (0.03% in drinking water for 16 days) induced-hypothyroid adult female rats. The intromission threshold for induction of pseudopregnancy also was examined to evaluate the PRL response to coital stimulation in hypothyroid rats. Hypothyroidism in adult female rats did not affect TIDA neuronal activity as measured by tyrosine hydroxylase activity (DOPA accumulation 30 min after administration of m-hydroxybenzylhydrazine dihydrochloride, 100 mg/kg, i.p.) in the stalk-median eminence compared with that in euthyroid rats, whereas pituitary concentration of VIP was dramatically increased. Plasma concentration of PRL was higher at 1100 h of proestrus and estrus in hypothyroid rats as compared with that of euthyroid rats. The proportion of female rats exhibiting pseudopregnancy was higher in hypothyroid animals (100%) receiving seven intromissions than in euthyroid animals (43%). Administration of L-thyroxine in hypothyroid rats decreased the proportion of pseudopregnancy (40%) to the level of euthyroid animals. These results indicate that the increased level of pituitary VIP probably affects PRL secretion in a paracrine or autocrine manner and account for the hyperprolactinemia induced in hy pothyroid female rats. No role for TIDA neurons in PRL elevation can be ascribed. A decrease in the intromission threshold for induction of pseudopregnancy might be due to increased levels of PRL in hypothyroid female rats. (C) 2000 Elsevier Science Inc. All rights reserved.

The effects of intracerebroventricular (10 ng/rat) or intravenous (10 or 40 mu g/15 min/rat) administration of salmon calcitonin (sCT) on the prolactin (PRL) response to suckling and the activity of tyrosine hydroxylase (TH) were examined in lactating rats. Plasma concentration of PRL increased dramatically in control rats after the onset of the suckling stimulus, while administration of sCT resulted in inhibition of PRL response to suckling. The action of sCT was much more effective with intracerebroventricular administration, which totally blocked PRL release, compared to intravenous administration. The intracerebroventricular administration of sCT increased TH activity of tuberoinfundibular dopamine neuron (TIDA) in the stalk-median eminence, as measured by DOPA accumulation, while completely suppressing the PRL response to suckling. Injection of alpha-methyl-rho-tyrosine (a-MT; 50 mg/kg), an inhibitor of TH and thus dopamine synthesis, increased PRL levels, and suckling caused a further increase in plasma concentrations of PRL, Injection of sCT (intracerebroventricularly) did not inhibit the PRL response to suckling in the presence of a depletion of dopamine. These results suggest that sCT inhibition of PRL secretion in lactating rats is mediated mainly by TIDA neurons without involvement of other neuroendocrine mechanisms. Copyright (C) 2000 S. Karger AG, Basel.

The hypothesis that genetic factors influence behavioral effects was tested in rats exposed prenatally to methylazoxymethanol (MAM). We examined whether baseline behavior is an important factor influencing behavioral effects, and whether a behaviorally selected strain was useful for study of neurobehavioral teratology. Pregnant high- and low-avoidance animals (HAAs and LAAs) of the Hatano strain, selectively bred for high and low shuttlebox avoidance responses, respectively, were given an IP injection of a low dose of MAM (15 mg/kg) on day 14 of gestation. The offspring of these animals were subjected to behavioral tests for locomotor activity (running-wheel and open-field tests) and learning ability (Biel maze and shuttlebox avoidance tests). There were no significant effects of MAM on running-wheel activity or shuttlebox avoidance learning, whereas the number of errors in the Biel maze was increased in the MAM offspring of both strains. interestingly, open-field activity of the MAM offspring was markedly decreased in LAAs but not in HAAs. Therefore, an additional experiment was performed to determine plasma levels of ACTH and corticosterone following open-field exposure, When compared to control offspring of the respective strains, plasma levels of ACTH and corticosterone were not altered by prenatal MAM treatment in LAAs. Instead, the MAM offspring in HAAs exhibited decreased ACTH levels in absence of behavioral alterations. These results demonstrated that prenatal exposure to low doses of MAM may alter postnatal behavior and endocrine response of the offspring, although to a differing degree in HAAs and LAAs. Our observations suggested that behaviorally selected strains are sensitive to neurobehavioral teratogens such as MAM. (C) 2000 Elsevier Science Inc. All rights reserved.

in the present study, the effects of dexamethasone on follicle-stimulating hormone (FSH) secretion in immature female rats were investigated. Dexamethasone increased the selective secretion of FSH and decreased plasma concentrations of inhibin in immature female rats. The effects of dexamethasone on FSH secretion were not confirmed in rats treated with ovariectomy or immunoneutralization against inhibin. In addition to the direct effect of dexamethasone on FSH synthesis in gonadotrophs, the present study has clearly demonstrated that the increased level of FSH in dexamethasone-treated rats is mediated by suppression of ovarian function, especially by the inhibition of inhibin secretion. (C) 1999 Elsevier Science B.V. All rights reserved.

in the present study, the effects of dexamethasone on follicle-stimulating hormone (FSH) secretion in immature female rats were investigated. Dexamethasone increased the selective secretion of FSH and decreased plasma concentrations of inhibin in immature female rats. The effects of dexamethasone on FSH secretion were not confirmed in rats treated with ovariectomy or immunoneutralization against inhibin. In addition to the direct effect of dexamethasone on FSH synthesis in gonadotrophs, the present study has clearly demonstrated that the increased level of FSH in dexamethasone-treated rats is mediated by suppression of ovarian function, especially by the inhibition of inhibin secretion. (C) 1999 Elsevier Science B.V. All rights reserved.

Having successfully bred for high- and low-avoidance rats (HAA and LAA, respectively) on a shuttlebox task, we performed three experiments designed to identify factors which might be related to the phenotypic differences seen in avoidance behavior. In experiment 1, shuttlebox behavior was measured to determine whether the phenotypic difference was activity related. In terms of intertrial responses, there was no difference between HAA and LAA rats in locomotor activity during the conditioning process. Experiment 2 compared adrenal weights of HAA and LAA rats at ii weeks of age. The observation that the adrenal glands were heavier in HAA than in LAA rats suggested that these strains might differ in aspects of endocrine response. In experiment 3, plasma levels of ACTH and corticosterone were determined during early escape/avoidance acquisition in the shuttlebox. Plasma levels of ACTH after the shuttlebox testing were higher in HAA than in LAA rats. There was no difference between the two strains in plasma levels of corticosterone after testing, possibly due to a ceiling effect. These results suggest that the phenotypic differences in the acquisition of avoidance behavior of HAA and LAA rats may be related to different endocrine responses, rather than to locomotor activity.

To determine the source of circulating inhibin and estradiol-17 beta during the estrous cycle in mares, the cellular localization of the inhibin alpha, beta(A), and beta(B) subunits and aromatase in the ovary was determined by immunohistochemistry. Concentrations of immunoreactive (ir-) inhibin, estradiol-17 beta, progesterone, LH, and FSH in peripheral blood were also measured during the estrous cycle in mares. Immunohistochemically, inhibin alpha subunits were localized in the granulosa cells of small and large follicles and in the theca interna cells of large follicles, whereas inhibin beta(A) and beta(B) subunits were localized in the granulosa cells and in the theca interna cells of Targe follicles. On the other hand, aromatase was restricted to only the granulosa cells of large follicles, Plasma ir-inhibin concentrations began to increase 9 days before ovulation; they remained high until 2 days before ovulation, after which they decreased when the LH surge was initiated. Thereafter, a further sharp rise in circulating ir-inhibin concentrations occurred during the process of ovulation, followed by a second abrupt decline. After the decline, plasma concentrations of ir-inhibin remained low during the luteal phase. Plasma estradiol-17 beta concentrations followed a profile similar to that of ir-inhibin, except during ovulation, and these two hormones were positively correlated throughout the estrous cycle. Plasma FSH concentrations were inversely related to ir-inhibin and estradiol-17 beta. These findings suggest that the dimeric inhibin is mainly secreted by the granulosa cells and the theca cells of large follicles; granulosa cells of small follicles may secrete inhibin cu subunit, and estradiol-17 beta is secreted by the granulosa cells of only large follicles in mares.

The effect of hypothyroidism on adrenals and gonads in adult female rats was investigated throughout the estrous cycle. Hypothyroidism was induced by administration of 4-Methyl-2-thiouracil (Thiouracil) in the drinking water. The weight of ovaries and adrenals, and the plasma levels of corticosterone decreased in hypothyroid rats as compared with euthyroid rats throughout the estrous cycle. Hypothyroidism resulted in decreased concentrations of plasma LH on the day of diestrus and proestrus, whereas the plasma concentrations of prolactin and progesterone increased as compared with euthyroid rats. The weight of uteri and plasma concentrations of estradiol decreased during the day of diestrus and proestrus in hypothyroid rats as compared with euthyroid rats. To further clarify the dysfunction of hypothalamo-hypophysial-adrenal axis in hypothyroid rats, animals were stressed by immobilization for 3 hr. In hypothyroid rats, a marked increase in plasma levels of ACTH in response to immobilization stress was observed compared to euthyroid control, whereas increases in plasma concentrations of corticosterone were much smaller in hypothyroid than euthyroid rats. These results clearly indicate that hypothyroidism causes both gonadal and adrenal disturbances in adult female rats. The increased concentrations of plasma progesterone may be due to hypersecretion of prolactin during the day of proestrus and estrus, which in turn result in disruption of the estrous cycle.

The effect of hypothyroidism on adrenals and gonads in adult female rats was investigated throughout the estrous cycle. Hypothyroidism was induced by administration of 4-Methyl-2-thiouracil (Thiouracil) in the drinking water. The weight of ovaries and adrenals, and the plasma levels of corticosterone decreased in hypothyroid rats as compared with euthyroid rats throughout the estrous cycle. Hypothyroidism resulted in decreased concentrations of plasma LH on the day of diestrus and proestrus, whereas the plasma concentrations of prolactin and progesterone increased as compared with euthyroid rats. The weight of uteri and plasma concentrations of estradiol decreased during the day of diestrus and proestrus in hypothyroid rats as compared with euthyroid rats. To further clarify the dysfunction of hypothalamo-hypophysial-adrenal axis in hypothyroid rats, animals were stressed by immobilization for 3 hr. In hypothyroid rats, a marked increase in plasma levels of ACTH in response to immobilization stress was observed compared to euthyroid control, whereas increases in plasma concentrations of corticosterone were much smaller in hypothyroid than euthyroid rats. These results clearly indicate that hypothyroidism causes both gonadal and adrenal disturbances in adult female rats. The increased concentrations of plasma progesterone may be due to hypersecretion of prolactin during the day of proestrus and estrus, which in turn result in disruption of the estrous cycle.

Male copulatory behavior and the function of the hypothalamo-hypophysial-gonadal axis in hypothyroid male rats were investigated in the present study. Hypothyroidism was induced by thyroidectomy or thiouracil. In male copulatory behavior test, intromission latencies in hypothyroid rats were significantly longer than those in euthyroid rats and ejaculation frequencies were reduced in hypothyroid male rats compared to control rats without reduction of plasma concentrations of testosterone. These changes in copulatory behavior in hypethyroid male rats were restored to control levels by administration of T4 (5 mu g/rat). Hypothyroidism decreased adrenal weights, and basal and peak concentrations of corticosterone during diurnal variation, whereas it increased peak concentrations of ACTH in adult male rats. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH. The adrenal disturbance observed in hypothyroid rats may affect male copulatory behavior.

Male copulatory behavior and the function of the hypothalamo-hypophysial-gonadal axis in hypothyroid male rats were investigated in the present study. Hypothyroidism was induced by thyroidectomy or thiouracil. In male copulatory behavior test, intromission latencies in hypothyroid rats were significantly longer than those in euthyroid rats and ejaculation frequencies were reduced in hypothyroid male rats compared to control rats without reduction of plasma concentrations of testosterone. These changes in copulatory behavior in hypethyroid male rats were restored to control levels by administration of T4 (5 mu g/rat). Hypothyroidism decreased adrenal weights, and basal and peak concentrations of corticosterone during diurnal variation, whereas it increased peak concentrations of ACTH in adult male rats. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH. The adrenal disturbance observed in hypothyroid rats may affect male copulatory behavior.

The relationship between hypothyroidism and disturbance of the hypothalamo-hypophysial-adrenal axis was investigated using adult male rats. Hypothyroidism was produced by administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Hypothyroidism decreased adrenal weights to 57% of controls and plasma concentrations of corticosterone to 48% of controls. The changes in the weight of adrenals recovered to control levels by administration of thyroxine. The pituitary responsiveness to corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) for ACTH release markedly increased in hypothyroid rats as compared with euthyroid rats. In vivo release of CRH and AVP in median eminence significantly increased in hypothyroid rats as compared with euthyroid rats. There were no significant differences in hypothalamic concentrations of CRH and AVP. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of ACTH mediated by increases in synthesis of CRH and AVP in the hypothalamus.

Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouracil-treated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH.

Adult male rats received pituitary transplantations to induce hyperprolactinemia. Some of those had bromocriptine (CB-154) treatment, and the other had vehicle (saline) as control. The grafted animals with vehicle exhibited significantly more suppression than sham operated animals. While the hyperprolactinemic rats treated with CB-154 showed no significantly more suppression of copulatory behavior than sham operated control. In the grafted animal without CB-154 treatment, the concentration of serum PRL was significantly higher than in sham operated controls. There were no significant differences in adrenal weight and serum levels of gonadotropin between grafted and control groups. These results may imply that PRL has direct actions on central nerveous system (CNS) and inhibits copulatory behavior in hyperprolactinemic male rats.

下垂体移植雄ラットにbromocriptine (CB-154) を投与し, 対照群にはvehicle (生理食塩水) を投与して交尾行動の観察を行った。高プロラクチン血症群では偽手術群と比べて交尾行動の有意な抑制が認められた。一方, CB-154処置群では偽手術群と比べて交尾行動の有意な抑制は認められなかった。下垂体を移植し生理食塩水を投与した群では偽手術群に比べて血清プロラクチン濃度が有意 (P<0.05) に上昇した。下垂体移植群と偽手術群の間には副腎重量と性腺刺激ホルモンの血清濃度において有意差は認められなかった。これらの結果はプロラクチンが中枢神経系に直接作用し, 交尾行動を抑制することを示唆するものと思われる。

糖尿病男性の性機能障害については良く知られているが, 女性に関しては現在のところ明確な回答が得られていない。最近, streptozotocin誘発糖尿病雄ラットに交尾行動の障害が認められている。今回, streptozotocin誘発糖尿病雌ラットの性行動について検討した結果, 雄と同様にロードシス行動の抑制が観察された。