Interactions of prostaglandin E1 (PGE1) and LRH on anterior pituitary function

Numerous biochemical pathways influence the synthesis and release of anterior pituitary hormones. Releasing factors extracted from the hypothalamus and prostaglandins (PGs) appear to alter a common biochemical activity, adenyl cyclase, in pituitary cells. Luteinizing hormone releasing hormone (LRH), prostaglandin (PGE₁), 7 oxa-13-prostynoic acid and cycloheximide were tested for individual and interacting effects on the in vitro release of FSH, LH and prolactin from hemipituitaries of 15 day old female rats. LRH (10 ng/ml) consistently released both LH and FSH in all in vitro experiments and inhibited prolactin release in 1 of 2 experiments. Lower concentrations (5 and 1 ng/ml) also stimulated LH and FSH release but did not influence prolactin release. Concurrent depletion of stored LH and FSH in the gland was observed. PGE₁ in a 6.5 hour incubation increased the storage of LH within the gland in the absence of LRH. In a 1.5 hour incubation in the presence of LRH, storage of LH was also increased. PGE₁ had no effect on LH and FSH release; however, in 1 of 2 experiments it stimulated prolactin release in the absence of LRH. Prostynoic acid stimulated LH and FSH release but did not synergize with LRH action in the same tissue. Cycloheximide did not affect LH release during the first 30 minutes of incubation; however, the release during the subsequent 1 hour was significantly inhibited. Similar tissue also exposed to cycloheximide was still responsive to LRH during the latter 1 hour incubation period. Cycloheximide had no effect on prolactin storage and release from the same tissue.     

Interactions of prostaglandin E1 (PGE1) and LRH on anterior pituitary function

Numerous biochemical pathways influence the synthesis and release of anterior pituitary hormones. Releasing factors extracted from the hypothalamus and prostaglandins (PGs) appear to alter a common biochemical activity, adenyl cyclase, in pituitary cells. Luteinizing hormone releasing hormone (LRH), prostaglandin (PGE₁), 7 oxa-13-prostynoic acid and cycloheximide were tested for individual and interacting effects on the $\text{in vitro}$ release of FSH, LH and prolactin from hemipituitaries of 15 day old female rats. LRH (10 ng/ml) consistently released both LH and FSH in all $\text{in vitro}$ experiments and inhibited prolactin release in 1 of 2 experiments. Lower concentrations (5 and 1 ng/ml) also stimulated LH and FSH release but did not influence prolactin release. Concurrent depletion of stored LH and FSH in the gland was observed. PGE₁ in a 6.5 hour incubation increased the storage of LH within the gland in the absence of LRH. In a 1.5 hour incubation in the presence of LRH, storage of LH was also increased. PGE₁ had no effect on LH and FSH release; however, in 1 of 2 experiments it stimulated prolactin release in the absence of LRH. Prostynoic acid stimulated LH and FSH release but did not synergize with LRH action in the same tissue. Cycloheximide did not affect LH release during the first 30 minutes of incubation; however, the release during the subsequent 1 hour was significantly inhibited. Similar tissue also exposed to cycloheximide was still responsive to LRH during the latter 1 hour incubation period. Cycloheximide had no effect on prolactin storage and release from the same tissue.     

Arginine Vasotocin: Structure-Activity Relationships and Influence on Gonadal Growth and Function

When AVT (arginine vasotocin) was given neonatally during theperiod when the brain is undergoing sexual differentiation,increased growth of the reproductive organs was observed inadulthood. Injection of AVT after this neonatal period in immatureanimals led to diminished growth of the accessory organs andin some cases the gonads themselves. The hypertrophic responseof the in situ ovary in adult mice following unilateral ovariectomy(UO) was inhibited in a dose-related manner by a single intraperitonealinjection of freshly prepared AVT. Much less AVT was requiredfor this response when injected into the third ventricle. Afterintraperitoneal injection, arginine vasopressin (AVP), lysinevasopressin (LVP), and 4-leucine vasotocin (4-leu-AVT) alsoinhibited compensatory ovarian hypertrophy whereas oxytocindid not. The commonality in die structure of these antigonadotrophicpeptides include a closed ring and a basic amino acid in position8. After opening the disulfide bond of these nonapeptides withmercaptoethanol, a single injection of the reduced AVT, AVP,LVP, or 4-leu-AVT into UO mice causes exaggerated hypertrophyof the remaining ovary. When added with leuteinizing hormone-releasinghormone (LRH) to culture medium containing hemipituitaries fromcastrated estrogen-progesterone primed female rats, AVT significantlyincreased the release of radioimmunoassayable LH above thatdue to LRH alone. AVT might interact at all levels of the hypothalamo-hypophysealgonadalaxis.     

Action of luteinizing hormone-releasing hormone and synthesis of prostaglandin in the pituitary gland.

The possibility that prostaglandin E2 (PGE2) may play a role in luteinizing hormone (LH) release was examined using an in vitro model. Addition of luteinizing hormone-releasing hormone (LH-RH) to the culture medium stimulated cyclic AMP accumulation and LH-release by incubated hemipituitaries, but did not affect the level of PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 content in the pituitary, but did not impair the stimulatory action of LH-RH on either cyclic AMP accumulation or LH-release. Flufenamic acid on its own caused LH-release, but the drug abolished the effect of LH-RH on cyclic AMP accumulation. The mechanism of this action of flufenamic acid is not understood. It is concluded that the stimulatory action of LH-RH on pituitary cyclic AMP production and LH release is not mediated by prostaglandins.     

Action of luteinizing hormone-releasing hormone and synthesis of prostaglandin in the pituitary gland

The possibility that prostaglandin E₂ (PGE₂) may play a role in luteinizing hormone (LH) release was examined using an model. Addition of luteinizing hormone-releasing hormone (LH-RH) to the culture medium stimulated cyclic AMP accumulation and LH-release by incubated hemipituitaries, but did not affect the level of PGE₂ or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE₂ content in the pituitary, but did not impair the stimulatory action of LH-RH on either cyclic AMP accumulation or LH-release. Flufenamic acid on its own caused LH-release, but the drug abolished the effect of LH-RH on cyclic AMP accumulation. The mechanism of this action of flufenamic acid is not understood.It is concluded that the stimulatory action of LH-RH on pituitary cyclic AMP production and LH release is not mediated by prostaglandins.     

Enkephalins and pituitary hormone release: modification of responsiveness to LHRH.

An intraperitoneal injection of leucine-enkephalin into rats stimulates gonadotropin and prolactin release. To elucidate the mechanism of this releasing property of leucine-enkephalin, rat hemipituitaries were incubated with either enkephalin alone or enkephalin in combination with OHRH. Enkephalin alone had no effect on LH or prolactin release in vitro but potentiated the LH response to LHRH. Neither leucine-enkephalin nor LHRH alone had an effect on GH release; however, when combined, a GH response to LHRH occurred. These results suggest that leucine-enkephalin can modify the pituitary responsiveness to certain hypothalamic releasing hormones by a direct pituitary action.     

Maintenance of gonadotrophs in pituitary autografts under the kidney capsules of female rats given sex hormones or LRH

Female Sprague-Dawley rats were hypophysectomized and the anterior pituitary gland was immediately placed under the kidney capsule. For 1 week after surgery, groups of pituitary autograft-bearing animals were treated with twice-daily injections of estradiol 17 beta (E), progesterone (P), estradiol 17 beta and progesterone (EP), or luteinizing hormone-releasing hormone (LRH). Within 2--4 hours following the last injection, the pituitary grafts were removed and placed into organ culture. They were maintained in culture with or without added LRH (10(-7) M) for 1 hour at 37 degrees C. The culture media were then frozen for later radioimmunoassay of FSH and LH. The tissues were kept in culture for an additional 24 hours, at which time they were fixed and prepared for immunocytochemistry or electron microscopy. Results showed that treatment of the animals with E, EP, or LRH enhanced the release of FSH and LH into the culture media, and that the release of these hormones was increased further by acute incubation with LRH. The ultrastructure of the gonadotrophs was well maintained by treating the animals with E or the combination of E and P or with LRH. Graft tissue from animals treated with LRH, which was incubated subsequently for 24 hours with LRH, showed the best maintenance of gonadotroph morphology. This experimental procedure should be useful for obtaining gonadotrophs for use in establishing gonadotroph cell lines.     

Menstrual disturbances in chronic renal failure.

Twelve female patients undergoing intermittent hemodialysis (HD) and 5 females posttransplantation (PT) were studied. All the HD patients had menstrual disturbances and 5 had galactorrhea. The mean basal LH level was significantly elevated (p less than .05) in patients on HD compared to normal controls, but the mean LH response to luteinizing hormone releasing hormone (LRH) was not significantly different from the control group. Mean basal FSH and the FSH response to LRH was normal. In the PT pateints the LH response to LRH was significantly greater at 120 min when compared to normal females. In the HD group the serum 17B estradiol, progesterone and testosterone levels were significantly lower than in the controls but in the PT group only testosterone levels were significantly lower. These results differ from those previously found in uremic males. Elevated prolactin levels were found in the patients on hemodialysis and correlated well with the presence of galactorrhea. These was no correlation between the elevated prolactin levels and amenorrhea in the patients on hemodialysis but one PT patient with amenorrhea had elevated prolactin levels.     

Effects of hyperprolactinemia on the control of luteinizing hormone and follicle-stimulating hormone secretion in the male rat

Experiments were conducted to determine the effects of acute hyperprolactinemia (hyperPRL) on the control of luteinizing hormone and follicle-stimulating hormone secretion in male rats. Exposure to elevated levels of prolactin from the time of castration (1 mg ovine prolactin 2 X daily) greatly attenuated the post-castration rise in LH observed 3 days after castration. By 7 days after castration, LH concentrations in the prolactin-treated animals approached the levels observed in control animals. HyperPRL had no effect on the postcastration rise in FSH. Pituitary responsiveness to gonadotropin hormone-releasing hormone (GnRH), as assessed by LH responses to an i.v. bolus of 25 ng GnRH, was only minimally effected by hperPRL at 3 and 7 days postcastration. LH responses were similar at all time points after GnRH in control and prolactin-treated animals, except for the peak LH responses, which were significantly smaller in the prolactin-treated animals. The effects of hyperPRL were examined further by exposing hemipituitaries in vitro from male rats to 6-min pulses of GnRH (5 ng/ml) every 30 min for 4 h. HyperPRL had no effect on basal LH release in vitro, on GnRH-stimulated LH release, or on pituitary LH concentrations in hemipituitaries from animals that were intact, 3 days postcastration, or 7 days postcastration. However, net GnRH-stimulated release of FSH was significantly higher by pituitaries from hyperprolactinemic, castrated males. To assess indirectly the effects of hyperPRL on GnRH release, males were subjected to electrical stimulation of the arcuate nucleus/median eminence (ARC/ME) 3 days postcastration. The presence of elevated levels of prolactin not only suppressed basal LH secretion but reduced the LH responses to electrical stimulation by 50% when compared to the LH responses in control castrated males. These results suggest that acute hyperPRL suppresses LH secretion but not FSH secretion. Although pituitary responsiveness is somewhat attenuated in hyperprolactinemic males, as assessed in vivo, it is normal when pituitaries are exposed to adequate amounts of GnRH in vitro. Thus, the effects of hyperPRL on pituitary responsiveness appear to be minimal, especially if the pituitary is exposed to an adequate GnRH stimulus. The suppression of basal LH secretion in vivo most likely reflects inadequate endogenous GnRH secretion. The greatly reduced LH responses after electrical stimulation in hyperprolactinemic males exposed to prolactin suggest further that hyperPRL suppresses GnRH secretion.     

beta-(-4 Chlorophenyl) GABA (baclofen) inhibits prolactin and thyrotropin release by acting on the rat brain

Baclofen, a GABA B agonist, inhibits prolactin release due to different kinds of stress. In the present study its effect was evaluated in several endocrine experimental situations to explore the specificity of this effect, as well as the site of action of the drug. Baclofen significantly inhibited prolactin and thyrotropin outputs induced by 25 min of suckling, without altering milk ejection or LH secretion. The effect was also tested in median eminence-lesioned rats and in in vitro incubations. Baclofen did not modify prolactin levels in rats in which brain control of the pituitary secretion was eliminated by destruction of the median eminence, and it did not inhibit prolactin or thyrotropin secretion from incubated hemipituitaries. It is postulated that baclofen inhibits prolactin and thyrotropin secretion by acting on GABA B receptors related to the brain control of pituitary secretion.     

Monolayer cultures of dispersed cells from bovine anterior pituitary: responses to synthetic hypophysiotropic peptides.

Cells were dispersed from bovine anterior pituitary glands, by digestion with collagenase, and cultured. After 4 days the cell monolayers were incubated with fresh medium containing synthetic hypophysiotropic peptides for 2, 6, or 20 h, and hormone released into the medium was estimated by radioimmunoassay. After 2 h, thyroid releasing hormone (TRH) stimulated the release of thyroid-stimulating hormone (TSH) up to eightfold, and of prolactin (PRL) and follicle-stimulating hormone (FSH) about twofold at a minimal effective concentration of 1 ng/ml; enhanced growth hormone (GH) release was not apparent until 20 h, and release of luteinizing hormone (LH) and adrenocorticotrophic hormone (ACTH) was unaffected. Luteinizing hormone releasing hormone (LH-RH) enhanced release of LH maximally (three- to fourfold) during a 2 h incubation and was effective at 0.1 ng/ml; FSH release was significantly enhanced by about 50% above control level. Growth hormone release inhibiting hormone (GH-RIH)(somatostatin) showed significant effects only in the 20 h incubation; GH release was inhibited by 50% and release of PRL was slightly, but significantly, enhanced. Pituitary cell monolayers apparently permit maximal expression of releasing activities inherent in the hypothalamic hormones.     

Lamprey GnRH-III acts on its putative receptor via nitric oxide to release follicle-stimulating hormone specifically

Lamprey gonadotropin-releasing hormone-III (l-GnRH-III), the putative follicle-stimulating hormone (FSH)-releasing factor (FSHRF), exerts a preferential FSH-releasing activity in rats both in vitro and in vivo. To test the hypothesis that l-GnRH-III acts on its own receptors to stimulate gonadotropin release, the functional activity of this peptide at mammalian (m) leutinizing hormone (LH)RH receptors transfected to COS cells was tested. l-GnRH-III activated m-LHRH receptors only at a minimal effective concentration (MEC) of 10(-6) M, whereas m-LHRH was active at a MEC of 10(-9) M, at least 1,000 times less than that required for l-GnRH-III. In 4-day monolayer cultured cells, l-GnRH-III was similarly extremely weak in releasing either LH or FSH, and, in fact, it released LH at a lower concentration (10(-7) M) than that required for FSH release (10(-6) M). In this assay, m-LHRH released both FSH and LH significantly at the lowest concentration tested (10(-10) M). On the other hand, l-GnRH-III had a high potency to selectively release FSH and not LH from hemipituitaries of male rats. The results suggest that the cultured cells were devoid of FSHRF receptors, thereby resulting in a pattern of FSH and LH release caused by the LHRH receptor. On the other hand, the putative FSH-releasing factor receptor accounts for the selective FSH release by l-GnRH-III when tested on hemipituitaries. Removal of calcium from the medium plus the addition of EGTA, a calcium chelator, suppressed the release of gonadotropins induced by either l-GnRH-III or LHRH, indicating that calcium is required for the action of either peptide. Previous results showed that sodium nitroprusside, a releaser of nitric oxide (NO), causes the release of both FSH and LH from hemipituitaries incubated in vitro. In the present experiments, a competitive inhibitor of NO synthase, L-NG-monomethyl-L-arginine (300 micro M) blocked the action of l-GnRH-III or partially purified FSHRF. The results indicate that l-GnRH-III and FSHRF act on putative FSHRF receptors by a calcium-dependent NO pathway.     

Site of action for β-endorphin-induced changes in plasma luteinizing hormone and prolactin in the ovariectomized rat

A number of sites have been hypothesized as loci at which opioid substances act to alter the secretion of luteinizing hormone (LH) and prolactin (PRL) (1–8). The aim of the present study was to determine the site(s) at which the opioid peptide β-endorphin (β-END) acts to influence plasma LH and PRL levels in the ovariectomized (OVX) rat. β-END, administered into the third ventricle of conscious OVX rats fitted with jugular catheters, significantly decreased plasma LH in doses ? 50 ng and increased PRL levels at all doses administered (10, 50, 100 and 250 ng) in a dose dependent fashion. To identify possible central nervous system sites of action, 250 ng β-END was unilaterally infused into various brain sites. Plasma LH was significantly decreased and plasma PRL significantly increased by infusions into the ventromedial hypothalamic area, the anterior hypothalamic area, and the preoptic-septal area. There was no significant effect of β-END infusions into the lateral hypothalamic area, amygdala, midbrain central gray, or caudate nucleus. When hemipituitaries of OVX rats were incubated $\text{in}$$\text{vitro}$ with β-END (10^?7M to 10^?5M), there was no suppression of basal or LHRH-induced LH release, nor was there any alteration of basal PRL release. It is concluded that β-END acts at a medial hypothalamic and/or preoptic-septal site and not the pituitary, to alter secretion of LH and PRL.     

Effect of prolonged incubation of male rat whole pituitary or pituitary-hypothalamus complex with testosterone on release of gonadotrophin and prolactin in vitro.

Investigations were undertaken to study the effect of in vitro addition of testosterone (0.3 mM) on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) by pituitary-hypothalamus complex (PHC) or the whole pituitary (PI) incubated for 72 hr, with incubation media changed every 24 hr. PHC or PI were from adult intact or castrated (7 days post castration) rats. The tissues incubated with or without testosterone were further exposed to 0.1 nM luteinizing hormone-releasing hormone (LHRH) for 4 hr. Incubation media and the pituitary were analyzed for PRL and gonadotrophin content. While PHC from normal and castrated rats released increasing amounts of LH with diminishing amounts of FSH and PRL at different periods of incubation, PI showed a decrease in the amounts of gonadotrophin and PRL released. Co-incubation of PHC or PI of intact or castrated rats with testosterone stimulated the release of LH and FSH during the first or second-24 hr incubation but inhibited the release of PRL in all the three incubations of 24 hr each. The extent of PRL inhibition increased with increasing incubation period. Testosterone had no effect on LHRH induced release of PRL but inhibited LHRH induced release of LH and FSH by pituitaries from constructs of normal rats. Testosterone reduced intrapituitary contents of PRL and FSH of intact and castrated rats. The data are interpreted to suggest that hypothalamus is essential for the maintenance of functional pituitary in vitro and that intrinsic differences exist in mechanisms regulating the secretion of LH, FSH and PRL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of central injection of bradykinin and bradykinin potentiating factor upon release of anterior pituitary hormones in ovariectomized female rats

The effects of third ventricular (IVT) injection of 25 μg of bradykinin (BK) upon plasma levels of LH, FSH, TSH, GH and prolactin were investigated in conscious ovariectomized female rats bearing indwelling jugular cannulae. Some animals were pretreated with bradykinin potentiating factor (BPF). Intravenous administration of BK had no effect upon hormone levels. IVT injection of BK significantly depressed plasma prolactin levels at 15 and 30 min post-drug, with levels returning to control values by 60 min. Pretreatment of animals with BPF (75 μg/3 μl) prolonged the prolactin suppression induced by BK for up to two hours. Plasma LH, FSH, TSH and GH levels in BK-rats were not significantly different from those of saline-injected animals at any time point measured. Neither BPF alone nor in conjunction with BK had any effects upon plasma levels of TSH; however, BK plus BPF suppressed FSH concentrations at 75 min post-BPF, while BPF alone appeared to increase GH levels at 45 min. In vitro incubation of hemipituitaries with 0.083, 0.83 or 8.33 μg/ml BK had no effect upon the release of LH, TSH or prolactin compared to control values. However, the secretion of GH and FSH was suppressed by the lowest dose of BK tested. These results suggest that BK may play a physiological inhibitory role in the regulation of prolactin, which can be augmented by preventing its degradation, i.e. via BPF. The effect of the peptide seems to be mediated by the CNS since neither intravenous injection of BK nor in vitro incubation of pituitaries with the peptide modified prolactin release.     

Effects of neuropeptide Y on LH, FSH and TSH release in male rats

These experiments were undertaken to investigate the effects of systemically administered neuropeptide Y (NPY) on gonadotropin secretion in the intact male rat and to determine whether the effects observed might be mediated by a direct action of NPY alone on the anterior pituitary gland (APG). Subcutaneous administration of 10 micrograms of NPY caused a greater than 2-fold increase in serum luteinizing hormone (LH) concentration at 15 min after injection but was without effect on serum follicle-stimulating hormone (FSH) or thyrotropin-stimulating hormone (TSH) levels. The addition of NPY (final concentrations of 10(-8) to 10(-11) M) or the structurally similar neuropeptide, rat pancreatic polypeptide, to culture medium containing hemi-APG did not alter the release of LH, FSH, or TSH. The results indicate that systemically administered NPY can elevate serum LH concentration in intact male rats. This effect does not appear to be due to NPY acting alone at the level of the APG.     

The role of domperidone in the regulation of prolactin release in rats

Effects of domperidone, a dopamine antagonist, on prolactin release in female rats were studied. Oral administration of domperidone for 14 days caused a significant increase in serum prolactin levels in mature female rats. The routes by which domperidone exerted its effects on prolactin release were studied by a in vitro incubation system using rat pituitary tissues. Pituitary halves were incubated with (1) domperidone, (2) dopamine, (3) dopamine plus domperidone, (4) hypothalamic extracts from rats which had been treated with control meal (control hypothalamic extract), (5) control hypothalamic extract plus domperidone, and with (6) hypothalamic extract from rats which had been treated with domperidone for 14 days (domperidone-treated hypothalamic extract). Pituitary halves, when incubated alone, released a significant amount of prolactin into the incubation medium after 24 hours incubation, which was completely inhibited by dopamine or control hypothalamic extract. The addition of domperidone could not reverse the inhibitory effect of dopamine or control hypothalamic extract. On the other hand, domperidone-treated hypothalamic extract showed no inhibitory effects on prolactin release. These results indicated that domperidone could increase serum prolactin levels in female rats by acting primarily at the hypothalamus.     

Effect of serotonin on the basal and gonadotrophin-releasing hormone-induced release of luteinizing hormone from rat pituitary glands in vitro

The effect of serotonin (5-HT) on the basal and gonadotrophin-releasing hormone (GnRH)-stimulated release of luteinizing hormone (LH) was studied in rat adenohypophysis in vitro. Anterior pituitary glands from ovariectomized rats were incubated for 1h in the presence of different doses of 5-HT (0.01 to 3 mumol/l). Serotonin added to the culture medium slightly dimished the basal release of LH and markedly inhibited the release of LH induced by GnRH. Responsiveness to GnRH (3 nmol/l) was significantly reduced, in a dose-dependent manner, by the simultaneous treatment of glands with 5-HT. Maximal inhibition to 65% of the response obtained with GnRH alone, was attained with 1 mumol/l 5-HT. The EC50 value was estimated to be about 1.9 X 10(-7) M. The inhibitory effect of 5-HT was evident within 30 min of incubation. Furthermore, 5-HT appear to exert a short-lasting action, since the rate of basal and GnRH-induced release of LH was reduced during the first hour of incubation, but after 2h the suppressive effects of 5-HT were no longer apparent. Methysergide, a serotonin receptor blocking agent, partially antagonized the inhibitory effect of 5-HT on LH release, either basal or GnRH-stimulated. This suggests that a receptor-mediated component may be involved in the mechanism of 5-HT action. The present results indicate that 5-HT can affect the release of LH by acting directly at the pituitary gland level.     

In vitro stimulation of prolactin release by vasoactive intestinal peptide

The effect of vasoactive intestinal peptide (VIP) on anterior pituitary hormone release was examined in a variety of in vitro preparations. Synthetic VIP was capable of stimulating increased prolactin (PRL) release from male rat hemipituitaries in doses as low as 10⁻⁹ M only when the enzyme inhibitor bacitracin was present in the incubation medium. Natural porcine VIP was similarly capable of stimulating PRL release, but only at higher doses (10⁻⁶ M). Additionally, synthetic VIP was capable of stimulating PRL release from dispersed anterior pituitary cells harvested from adult male and lactating female rats and from an enriched population of lactotrophs obtained by unit gravity sedimentation of similar dispersed cells from infantile female rats. No effect of VIP on luteinizing hormone, growth hormone or thyroid stimulating hormone release was seen. These findings taken in concert with the presence of VIP in the hypothalamus, pituitary and hypophyseal portal plasma of the rat suggest a physiological role for VIP in the control of PRL secretion.     

Catecholamine mechanisms in the feedback effects of estradiol benzoate on the release of LH and prolactin

The role of hypothalamic catecholamines and luteinizing hormone releasing hormone (LHRH) in the negative feedback effect of estradiol benzoate (EB) on luteinizing hormone (LH) release was studied in chronic ovariectomized rats. Administration of 10 micrograms EB decreased plasma LH levels and increased LHRH content in the medial basal hypothalamus (MBH) 1 day after injection. Inhibition of dopamine and norepinephrine synthesis with alpha-methyl-p-tyrosine (alpha-MT) reduced the LHRH content in the MBH in both oil- and EB-treated animals and partially reversed the decrease in plasma LH levels. Inhibition of norepinephrine synthesis with fusaric acid decreased LHRH content in both oil- and EB-treated rats but had no effect on plasma LH levels. The results suggest that at least a portion of the inhibitory effect of EB on LH release is due to the stimulation of an inhibitory dopaminergic mechanism which reduces LHRH release from the MBH. This feedback mechanism is apparently not susceptible to dopaminergic receptor blockade since administration of pimozide had no effect on LH levels. The stimulatory feedback effect of EB on prolactin release was studied in the same animals. alpha-MT and EB produced additive effects on plasma prolactin levels whereas fusaric acid blocked the EB-induced increase in plasma prolactin levels. Pimozide appeared to potentiate the effect of EB on prolactin release. The results reconfirm the possible role of noradrenergic neurons in the release of prolactin induced by EB and also suggest that EB stimulates a dopaminergic mechanism which is inhibitory to prolactin release but is normally masked by increased noradrenergic activity.