Effects of short photoperiod on the ability of golden hamster pituitaries to secrete prolactin and gonadotropins in vitro

Transfer of male golden (Syrian) hamsters from a 14L:10D (light:dark) to a 5L:19D photoperiod induced significant changes in pituitary function tested in vitro. Within 27 days after transfer to a 5L:19D photoperiod, basal prolactin (Prl) release was significantly depressed and response to dopamine (DA) was significantly enhanced as compared to Prl release by pituitaries from 14L: 10D hamsters. Follicle-stimulating hormone (FSH) release tended to be depressed after 9 or 27 days of 5L:19D exposure, but the effect was not significant. After 77 days of 5L:19D exposure, Prl release was further suppressed, while FSH release surpassed that seen in 14L:10D pituitaries. In vitro FSH response to luteinizing hormone releasing hormone (LHRH) was also enhanced at this time. After 15 weeks of exposure to a short photoperiod, FSH secretion was still elevated above control levels, but Prl release and Prl response to DA were no longer different from that of 14L: 10D controls. Secretion of luteinizing hormone (LH) in vitro, either basal or LHRH stimulated, was not affected by photoperiod at any time tested. From these results, we conclude that short photoperiod exposure does not reduce the pituitary's ability to secrete LH or FSH, although secretion of Prl is severely attenuated.     

Contrasting effects of pituitary adenylate cyclase activating polypeptide (PACAP) on in vivo and in vitro prolactin and growth hormone release in male rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is produced by hypothalamic neurons which terminate within the median eminence suggesting that it may be a hypophysiotropic hormone. However, little endocrine activity has been ascribed to the peptide. Therefore we studied the effects of PACAP on prolactin (Prl) release from dispersed cultivated rat pituitary cells in vitro using conventional cultures as well as the reverse hemolytic plaque assay (RHPA). Furthermore the effects of the peptide on in vitro GH release were assessed. In addition, the activity of the peptide on in vivo release of Prl and GH was studied in hypothalamus-lesioned animals. PACAP dose dependently inhibited Prl release form dispersed pituitary cells in both, monolayer cell cultures and the RHPA, whereas GH secretion was not affected. In hypothalamus-lesioned rats which have high Prl levels due to the absence of hypothalamic dopamine, PACAP further stimulated Prl release. Serum GH increased more than 20 fold in response to the intravenous PACAP infusion. Thus in vitro (inhibition of Prl release, no effect on GH release) and in vivo (stimulation of both hormones) experiments yielded contradicting effects of PACAP on pituitary hormone release. We suggest that PACAP may stimulate the release of a paracrine, yet unknown factor which in the intact pituitary overrides the direct inhibitory action of PACAP on the lactotropes. The same or another paracrine factor may also enhance in vivo GH release. In cell culture the paracrine factor is diluted by the medium. Therefore the peptide never reaches effective concentrations which are present within the intact pituitary tissue.     

Further evidence that prolactin does not affect gonadotropin release at pituitary level

In a primary monolayer cell culture of the anterior pituitary from mature male rats the effects of exogenous rPrl (rPrl exog.) and endogenously secreted rPrl (rPrl endog.) on basal and LHRH stimulated LH secretion were investigated. In pilot studies basal Prl- and LH secretion as well as influence of various LHRH concentrations (10(-1)-10(+3) ng/ml) on Prl- and LH release were observed. The influence of exogenous rPrl was studied at various concentrations (50-500 ng/ml) and with preincubation periods of 2 hrs and 6 hrs before starting LHRH stimulation. The dopamine agonist bromocriptine and the dopamine antagonist sulpirid were preferentially used to prove physiologic function of the cell system presented. Basal LH secretion started after a delay of 3 hrs, whereas basal Prl secretion began immediately showing a linear rise for 9 hrs. LHRH stimulation resulted in a non-linear dose and time dependent LH secretion. LHRH showed no influence on endogenous Prl (rPrl endog.) secretion of the mammotroph cells. Exogenous Prl (rPrl exog.) did not affect spontaneous Prl release excluding ultra short loop inhibition in this cell system. Furthermore, exogenous Prl had no effect on either basal or LHRH stimulated LH secretion even after a preincubation period of up to 6 hrs and at concentrations generally observed for prolactin secreting tumors. Bromocriptine suppressed endogenous Prl release and did not affect LH secretion. Sulpirid had no influence on either Prl or LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effects of cysteamine on neuroendocrine function

The action of cysteamine on anterior pituitary hormone secretion was studied in vivo using conscious, freely moving male rats and in vitro using anterior pituitary cells in monolayer culture. Administration of 500 micrograms cysteamine into the lateral cerebral ventricles of normal rats caused the complete inhibition of pulsatile GH secretion for a minimum of 6 h. This treatment also significantly decreased plasma concentrations of LH for at least 6 h in orchiectomized rat, TSH in short-term (0.5 month) thyroidectomized rats, and PRL in long-term (6 months) thyroidectomized rats. The in vivo stimulation of GH, LH, TSH and PRL with their respective releasing hormones 60 min after administration of cysteamine was not different from the response observed in rats pretreated with saline except for PRL where cysteamine pretreatment significantly inhibited the expected PRL increase. In vitro, 1 mM cysteamine decreased basal and TRH stimulated PRL release while not affecting basal or stimulated GH, LH, TSH and ACTH secretion. These data demonstrate the dramatic and wide-ranging effects of cysteamine on anterior pituitary hormone secretion. This action appears to be mediated through hypothalamic pathways for GH, LH and TSH and through a pituitary pathway for PRL.     

Serotonergic influences on pituitary gland and hypothalamic induction of prolactin and luteinizing hormone release in the young turkey (Meleagris gallopavo)

Primary anterior pituitary cell cultures were utilized to study the influence of serotonin (5-HT) directly on the pituitary. Cells incubated with 10(-5) and 10(-4) M 5-HT exhibited a significant prolactin (Prl) release, whereas cells incubated with 10(-10) to 10(-6) M 5-HT did not. Cells incubated with 10(-10) to 10(-4) M quipazine (5-HT agonist) or methysergide (MES; 5-HT antagonist) did not release Prl in amounts greater/less (P greater than 0.01) than spontaneous release. Luteinizing hormone (LH) release from cells incubated in the presence of 5-HT, quipazine, or MES was similar to spontaneous release. The hypothalamic extract-induced Prl and LH release from cells was not influenced by quipazine, but Prl release was diminished in a dose-related fashion by MES. The influence of 5-HT on hypothalamic induction of Prl and LH release was investigated utilizing in vitro culture of hypothalamic fragments (HF). Media samples from HF incubated with 10(-6) and 10(-4) M 5-HT induced a release of Prl. Media samples from HF incubated with 10(-4) M MES induced less Prl release than media samples from control fragments. When HF were incubated with both 10(-4) M 5-HT and 10(-4) M MES, the expected 5-HT-mediated Prl release was not evident. These culturing situations had no influence on LH release. In vitro Prl release from pituitary cells of the young turkey was stimulated through 5-HT activity at the hypothalamus, but not by direct 5-HT action on the pituitary cells.     

Temporal sequence of neuroendocrine events associated with the transfer of male golden hamsters from a stimulatory to a nonstimulatory photoperiod

The transfer of male golden hamsters from long day (LD) to short day (SD) conditions results in gonadal atrophy within 8 weeks and significant reductions in LH, FSH, and prolactin (Prl) secretion as early as 4 weeks. Changes in hypothalamic neurotransmitter metabolism precede these changes in pituitary hormone secretion. Thus median eminence norepinephrine (NE) turnover declines steadily after SD exposure, although the differences as compared to turnover in LD hamsters are not significant until Week 4. Median eminence dopamine (DA) turnover is reduced significantly within 1 week. Turnover of NE and DA in the medial basal hypothalamus also changes significantly within 1 or 2 weeks of SD exposure, but the changes are not maintained through Week 8, despite continued reductions in levels of circulating LH, FSH, and Prl. Reductions in median eminence NE metabolism appear to be responsible for the decrease in LH and FSH release. Initial decreases in Prl release appear to be hypothalamic in origin, but the hypothalamic factor(s) responsible for this change is not evident. An increase in inhibitory input from tuberoinfundibular dopaminergic neurons is clearly not involved.     

多巴胺、雌二醇及睾酮对虎纹蛙离体脑垂体促性腺激素分泌的影响

为了解虎纹蛙促性腺激素分泌的调节机理,用离体静态培育系统和放射免疫测定法,研究了多巴胺（ＤＡ）、雌二醇（Ｅ２）和睾酮（Ｔ）对雌性虎纹蛙离体脑垂体薄片促黄体激素（ＬＨ）和促卵泡激素（ＦＳＨ）分泌活动的影响。结果表明：０．１～１０μｍｏｌ／Ｌ的ＤＡ对成熟前期和冬眠期虎纹蛙离体脑垂体型薄片的ＬＨ及ＦＳＨ的释放都有抑制作用,并且随着ＤＡ浓度的增加,抑制作用逐渐增强。１和１０μｍｏｌ／Ｌ的Ｅ２显著刺激成熟前     

Evidence for dopaminergic regulation of prolactin and a luteotropic complex in the ferret

The role of dopaminergic agents in prolactin (Prl) release and the luteotrophic role of Prl and luteinizing hormone (LH) were investigated in pseudopregnant female ferrets. A single injection of the dopamine antagonist pimozide (0.63 mg/kg) resulted in a tenfold elevation of plasma Prl in anestrous females. Subcutaneous injection of pimozide on alternate days from Day 2 through Day 16 of pseudopregnancy elevated both Prl and progesterone levels. Daily treatment with the dopamine agonist 2 alpha-bromoergocryptine (bromocriptine, 4 mg/kg), from Day 2 through Day 16 of pseudopregnancy lowered levels of both plasma Prl and progesterone. Neither pimozide nor bromocriptine had a direct effect on progesterone secretion by luteal cells in vitro. Daily intraperitoneal administration of a monoclonal antibody against gonadotropin-releasing hormone from Day 2 through Day 10 of pseudopregnancy lowered both plasma LH and progesterone, but had no effect on plasma Prl concentrations. Daily administration of equine antisera against bovine LH or 100 IU of human chorionic gonadotrophin to pseudopregnant ferrets lowered progesterone levels. It is concluded that Prl release is influenced by dopaminergic compounds, and both Prl and LH are required for luteal maintenance in the ferret.     

Effects of in vivo pretreatment with D-Trp-6-LH-RH on prolactin and LH secretion by pituitary glands in vitro

In order to study a possible direct action of LH-RH analogs on the pituitary lactotrophs, we investigated the effect of long-term in vivo pretreatment with D-Trp-6-LH-RH on in vitro secretion of PRL and luteinizing hormone (LH) by the pituitary glands from male and female rats. In vivo pretreatment with D-Trp-6-LH-RH (50 micrograms/day, SC) for 15 days greatly reduced basal in vitro PRL release (p less than 0.01) in female, but not in male pituitary glands. TRH-stimulated PRL secretion was not affected by pretreatment with D-Trp-6-LH-RH in female rats, but was impaired in male pituitaries. Acute in vitro exposure to D-Trp-6-LH-RH did not modify PRL secretion by female pituitary glands pretreated in vivo with the analog. However, this same in vivo pretreatment greatly decreased PRL release from male pituitaries (p less than 0.01). Basal in vitro LH release by male pituitary glands was partially lowered by in vivo pretreatment with D-Trp-6-LH-RH, as compared to controls (p less than 0.01), while basal LH release in female pituitaries remained at control levels. Finally, D-Trp-6-LH-RH-induced stimulation of in vitro LH release was severely impaired in female pituitaries (p less than 0.01) but only slightly reduced in the males.     

Direct kisspeptin-10 stimulation on luteinizing hormone secretion from bovine and porcine anterior pituitary cells

Kisspeptins are peptide hormones encoded by the KiSS-1 gene and act as the principal positive regulator of the reproductive axis by directly stimulating gonadotropin-releasing hormone (GnRH) neuron activity. However, peripheral administration, as well as central administration, of kisspeptin stimulates luteinizing hormone (LH) secretion in some mammalian species. In order to evaluate the direct effects of kisspeptin-10 (the minimal kisspeptin sequence necessary for receptor activation) on LH secretion from bovine and porcine anterior pituitary (AP) cells, LH-releasing effects of kisspeptin-10 on AP cells were compared with GnRH in vitro. The AP cells were prepared from 1-month-old intact male calves, 8-month-old castrated male calves, or 6-month-old barrows, and then the cells were incubated for 2h with the peptides. The 1000 nM and 10,000 nM, but not lower concentrations, of kisspeptin-10 significantly stimulated LH secretion from the bovine AP cells (P<0.05). The 100 nM and 1000 nM, but not lower concentrations, of kisspeptin-10 significantly stimulated LH secretion from porcine AP cells (P<0.05). As 10nM of GnRH strongly stimulated LH secretion from all AP cells tested in this study, the present results suggest that kisspeptin-10 has a direct, but weak, stimulating effect on LH secretion in bovine and porcine AP cells. The present study is the first to examine the direct actions of kisspeptin on the bovine and porcine pituitary gland as far as we know. Kisspeptin might have other actions on the pituitary because the pituitary has multiple roles.     

Effect of selective removal of the adrenal medulla on female sexual development

The ovary and adenohypophysis of the rat contain beta-adrenergic receptors and respond to beta-adrenergic stimulation with hormone release. To determine the importance of the adrenal medulla as a source of adrenergic influences regulating prepubertal ovarian and pituitary function, a technique was developed to remove most of the adrenal medulla without compromising adrenocortical function. Medullectomy (MED) of 24-day-old female rats depressed both spontaneous diurnal changes in plasma epinephrine (EPI), and the EPI and norepinephrine (NE) response to decapitation, without affecting corticosterone (B) levels. Vaginal opening and first ovulation were delayed in MED rats. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were normal in MED rats, but those of growth hormone (GH) and prolactin (Prl) were depressed. MED reduced the ovarian weight response to pregnant mare's serum gonadotropin (PMSG) and the ovarian steroidal response to human chorionic gonadotropin (hCG) in vitro, but it did not affect ovarian beta-adrenergic receptors. Cultured granulosa cells, harvested from juvenile ovaries and primed in vitro with FSH, responded to nanomolar concentrations of EPI with progesterone (P) secretion. EPI also augmented hCG- and FSH-induced P secretion. The EPI effect was reproduced by Zinterol, a beta 2-adrenergic agonist and was prevented by propranolol, a beta-adrenergic antagonist. Blockade of alpha-adrenergic receptors with phentolamine was ineffective. It is suggested that EPI of adrenomedullary origin supports female prepubertal development by a) stimulating ovarian P secretion, b) favoring Prl and GH release and c) amplifying the stimulatory effect of low gonadotropin levels on ovarian steroidogenesis. The effects of EPI on ovarian function appear to be mediated by beta-adrenergic receptors of the beta 2 type.     

Different signaling in pig anterior pituitary cells by GnRH and its complexes with copper and nickel

Gonadotropin releasing hormone (GnRH) is an essential factor in the regulation of synthesis and release of pituitary gonadotropins. After binding to specific receptors and coupling with G proteins, it triggers the intracellular signaling involving the synthesis of inositol phosphates and diacylglycerol. Previously we have showed that certain metal complexes with GnRH, i.e. copper (Cu-GnRH) and nickel (Ni-GnRH) are able to bind to the GnRH receptors. The intracellular signalling of these complexes, however, has not been yet elucidated. In this experiment, the ability of the Cu-GnRH and Ni-GnRH complexes to modulate cAMP synthesis and phosphoinositols formation in the pig anterior pituitary cells in vitro was studied. The native GnRH and its metal complexes stimulated the luteinizing hormone (LH) release, but only the effect of Cu-GnRH was found to be a dose-dependent. The metal complexes did not significantly influence inositol phosphates accumulation, while their effect on cAMP synthesis was significantly more potent than that of GnRH alone. We conclude that the Cu-GnRH and Ni-GnRH complexes increase LH release in the porcine pituitary cells although their intracellular signaling is different from that of the native GnRH. It seems that metal complexes with GnRH deserve more attention in further studies.     

LH release by Cu and Ni salts and metal-GnRH complexes, in vitro

The present studies were undertaken to examine the effect of copper and nickel salts and their complexes with GnRH on LH release from the pig anterior pituitary cells in vitro. The potency of Cu-GnRH and Ni-GnRH binding to GnRH receptors with iodinated GnRH as a radioactive tracer was also verified. The incubation of pig pituitary cells with Cu and Ni acetate salts showed no effect of the studied ions on LH release at any concentration used. However, nickel salt at a lower dose (10(-10) and 10(-9) M) tended to decrease LH output. By contrast, the native GnRH as well as its metal complexes significantly stimulated LH release after three hours of treatment and Cu-GnRH was found to be the most effective. The results showed that Cu and Ni complexes with GnRH but not their acetate salts are effective in LH release from pig pituitary cells collected from adult female pigs.     

Pancreatic polypeptides affect luteinizing and growth hormone secretion in rats

We have examined the effects of third cerebroventricular (3V) injections of avian and bovine pancreatic polypeptide (APP and BPP) and the C-terminal hexapeptide amide of human PP (CHPP) on the secretion of anterior pituitary hormones in conscious ovariectomized rats. Injection of APP (2.0 micrograms; 472 pmoles) or BPP (5.0 micrograms; 1191 pmoles) decreased plasma levels of luteinizing hormone (LH) when compared to pre-injection levels in these animals or to saline-injected controls. The lower dose of BPP (0.5 micrograms; 119 pmoles) decreased plasma LH versus pre-injection levels and control animals, however, these effects diminished at later times. Plasma growth hormone (GH) also decreased following 3V injections of APP (2.0 micrograms) or BPP (5.0 micrograms). The lower dose of BPP (0.5 microgram) initially inhibited GH release, however, this effect was rapidly reversed and GH levels were significantly greater than those in controls at 60 and 120 min. Injections of BPP or APP did not alter prolactin (PRL) or thyroid stimulating hormone (TSH) secretion. Administration of 2.0 micrograms and 0.2 microgram of CHPP (2488 and 249 pmoles) produced no significant effects on plasma LH, GH, PRL or TSH. APP and BPP had no consistent effects on hormone secretion from dispersed anterior pituitary cells. The results indicate that APP and BPP exert potent central effects which inhibit LH and GH release from the pituitary gland.     

Role of arginine vasopressin in control of ACTH and LH release during stress

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.     

An increase of pituitary 3', 5' cyclic adenosine monophosphate produced by estradiol benzoate in vitro: possible implication of this increase in the secretion of luteinizing hormone.

In an attempt to study the site and mechanism of action of estrogen in producing positive feedback control, porcine anterior pituitary slices were incubated in vitro in the presence of estradiol benzoate (EB). EB elevated pituitary cyclic AMP concentration within 5 min and augmented pituitary release of luteinizing hormone (LH). The magnitude of increase of cyclic AMP and LH release was related to the doses of EB used. Also, luteinizing hormone releasing hormone (LH-RH) elevated pituitary cyclic AMP concentration and stimulated pituitary release of LH. The magnitude of increase of cyclic AMP and LH release was inversely related to the doses of LH-RH used. EB and LH-RH were additive in increasing cyclic AMP. Progesterone and clomiphene citrate interfered with an increase of pituitary cyclic AMP produced by EB, but did not significantly affect the basal level of pituitary cyclic AMP. Testosterone propionate, human chorionic gonadotropin and hexestrol were without effect on either basal or stimulated level of pituitary cyclic AMP. Since cyclic AMP and dibutyryl cyclic AMP (DBC) stimulated LH release, it is suggested that EB directly stimulates the release of LH by augmenting cyclic AMP synthesis in the anterior pituitary.     

Steroidal modulation of in vitro gonadotropin secretion in prepubertal and adult male Siberian hamsters

The effects of exogenous gonadal steroids, testosterone (T), and 17beta-estradiol (E(2)) upon the hypothalamo-pituitary-gonadal axis were reported to be different between prepubertal and adult Siberian hamsters. Utilizing an in vitro static culture system, we investigated if age-related differences in steroid responsiveness occurs at the pituitary. Prepubertal (20 days old) or adult (140 days old) male Siberian hamsters were implanted with 1 mm silastic capsules containing undiluted T, E(2) or cholesterol (Ch, control). After 15 days, pituitaries were removed, incubated in vitro, and subjected to the following treatments: two baseline measurements, one challenge with 10ng/ml of D-Lys(6)-gonadotropin-releasing hormone (GnRH), and three post-challenge washes. Fractions were collected every 30 minutes and measured for follicle-stimulating hormone (FSH) and luteinizing hormone (LH). T and E(2 )reduced basal secretion of LH and FSH in juveniles but not adults. In juveniles, E(2) increased GnRH-induced FSH and LH secretion, while T augmented GnRH-induced FSH secretion but attenuated GnRH-induced LH secretion. Steroid treatment had no effect on GnRH-stimulated LH or FSH release in adults. The only effect of steroid hormones upon adult pituitaries was the more rapid return of gonadotropin secretion to baseline levels following a GnRH challenge. These data suggest both basal and GnRH-induced gonadotropin secretion are more sensitive to steroid treatment in juvenile hamsters than adults. Further, differential steroidal regulation of FSH and LH at the level of the pituitary in juveniles might be a mechanism for the change in sensitivity to the negative effects of steroid hormones that occurs during the pubertal transition.     

Periventricular and suprachiasmatic lesion effects on photoperiodic responses of the hamster hypophyseal-gonadal axis

We examined the involvement of neural mechanisms within the suprachiasmatic nucleus (SCN) and periventricular area (PVA), and the role of prolactin (Prl) in control of endocrine function in short day-exposed Syrian hamsters. Hamsters bearing lesions of the SCN or PVA, hamsters implanted with an anterior pituitary under the kidney capsule to provide sustained Prl levels, and sham-operated hamsters were exposed to either 14L:10D or 8L:16D. After 9 wk, hamsters were sacrificed, and their testes and pituitaries were studied in vitro to assess their secretory capacity. SCN lesions and large periventricular lesions impinging on the paraventricular nucleus prevented testicular regression during short-day exposure. Small periventricular lesions and pituitary implants did not prevent gonadal regression in hamsters exposed to short days. Testis weights were positively correlated with basal and luteinizing hormone (LH)-stimulated androgen production in the control and lesioned groups; pituitary implants prevented the decline in androgen production in vitro in gonadally regressed animals. The relative in vitro pituitary response to gonadotropin-releasing hormone (GnRH) stimulation in control and lesioned groups was not reduced by short-day exposure. These data indicate that either axons coursing dorsally from the SCN or extra-SCN structures in the periventricular/paraventricular area are necessary for testicular regression in short photoperiods.     

Hormonal regulation of progesterone secretion by cultured mouse granulosa cells

Secretion of progesterone by granulosa cells from preovulatory follicles of mice was determined during 2 weeks of cell culture in the presence of androgens, estrogen and pituitary gonadotropins. Androstenedione (10(-7) M) and dihydrotestosterone (10(-7) M) stimulated (P less than 0.05) progesterone secretion during the first 11 days of culture. In contrast, 17 beta-estradiol (10(-11)-10(-7) M) did not alter (P greater than 0.10) progesterone secretion throughout the culture period. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) stimulated (P less than 0.01) the granulosa cells in a dose-dependent manner during the first few days of culture. This luteotropic effect was rapidly lost and at later times when FSH was not effective, LH suppressed (P less than 0.05) progesterone secretion. In the presence of prolactin (Prl) (1 microgram/ml), granulosa cells progressively secreted more progesterone during the first week of culture. After maximal stimulation on Days 7-9, progesterone secretion by Prl-treated cells began to decline, but the amount of steroid produced on Day 13 was still higher (P less than 0.05) than in control cultures. Androstenedione and Prl gave an additive effect on progesterone secretion during Days 3-5 of culture. Thereafter, the androgen, although stimulatory by itself, did not influence the luteotropic action of Prl. Unlike the early effect of androgens, 17 beta-estradiol acted synergistically with Prl to maintain maximal secretion of progesterone during the last 4 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation of endogenous opioid peptides and morphine to neuroendocrine functions.

Morphine and the endogenous opioid peptides (EOP) exert similar effects on the neuroendocrine system. When adminstered acutely, they stimulate growth hormone (GH), prolactin (PRL), and adrenocorticotropin (ACTH) release, and inhibit release of luteinizing hormone (LH), follicle stimulating hormone (FSH),and thyrotropin (TSH). Recent studies indicate that the EOP probably have a physiological role in regulating pituitary hormone secretion. Thus injection of naloxone (opiate antagonist) alone in rats resulted in a rapid fall in serum concentrations of GH and PRL, and a rise in serum LH and FSH, suggesting that the EOP help maintain basal secretion of these hormones. Prior administration of naloxone or naltrexon inhibited stress-induced PRL release, and elevated serum LH in castrated male rats to greater than normal castrate levels. Studies on the mechanisms of action of the EOP and morphine on hormone secretion indicate that they have no direct effect on the pituitary, but act via the hypothalamus. There is no evidence that the EOP or morphine alter the action of the hypothalamic hypophysiotropic hormones on pituitary hormone secretion; they probably act via hypothalamic neurotransmitters to influence release of the hypothalamic hormones into the pituitary portal vessels. Preliminary observations indicate that they may increase serotonin and decrease dopamine metabolism in the hypothalamus, which could account for practically all of their effects on pituitary hormone secretion.