Involvement of hypothalamic vasoactive intestinal polypeptide (VIP) in prolactin secretion induced by serotonin in rats

To study the possible involvement of hypothalamic vasoactive intestinal polypeptide (VIP) in regulating the secretion of prolactin (PRL), the effect of anti-VIP rabbit serum on serotonin (5-HT)-induced PRL release was examined in urethane-anesthetized male rats. Anti-VIP serum (AVS) or normal rabbit serum (NRS) was infused into a single hypophysial portal vessel of the rat for 40 min at a rate of 2 microliters/min with the aid of a fine glass cannula and 5-HT was injected into a lateral ventricle 10 min after the start of the infusion. Intraventricular injection of 5-HT (10 micrograms/rat) caused an increase in plasma PRL levels in control animals infused with NRS and 5-HT-induced PRL release was blunted in animals infused with AVS (mean +/- SE peak plasma PRL: 118.9 +/- 19.8 ng/ml vs 54.7 +/- 16.2 ng/ml, p less than 0.05). These findings suggest that the secretion of PRL induced by 5-HT is mediated, at least in part, by hypothalamic VIP release into the hypophysial portal blood in the rat.     

Augmentation, by naloxone, of the frequency and amplitude of LH-RH pulses in hypothalamo-hypophyseal portal blood in the castrated ram

The effect of naloxone administration on the LH-RH secretion in hypophyseal portal blood and LH secretion in peripheral blood was studied in four short term castrated rams (between 2 to 4 days after castration). For two animals (A and B) given a single naloxone injection, an increase of LH-RH pulse amplitude was observed (A, 22.3 to 80.5 pg/ml and B, 22.5 to 34.5 pg/ml) with only a small (nonsignificant) increase in LH-RH pulse frequency. For animals C and D given four injections of naloxone, both LH-RH pulse amplitudes and LH-RH pulse frequency were increased. Means of LH-RH pulse amplitude increase from 29.3 to 65.1 pg/ml and from 34.6 to 50.8 pg/ml for animals C and D respectively and the number of LH-RH pulses detected during the 3 hrs. before and after the first injection of naloxone were respectively 3 vs. 5 and 3 vs. 7. Whereas all LH pulses were preceded with a LH-RH pulse in animals A and B, after the multiple naloxone injections in animals C and D, a rapid LH-RH pulse frequency was associated with a sustained increment of LH secretion in peripheral blood in such a way that individual LH pulses were not clearly defined. The present report is the first documentation on naloxone increasing the release of LH-RH secretion in hypophyseal portal blood of conscious, unrestrained, short-term castrated rams. The results indicate: (1) that the opiate antagonist naloxone is able to increase both the amplitude and the frequency of LH-RH discharge by the hypothalamus and (2), when the LH-RH pulse frequency exceeds one pulse every 30 min., discrete LH secretory episodes are not observed in peripheral blood.     

Effects of pulsatile infusion of luteinizing hormone-releasing hormone on luteinizing hormone secretion and ovarian function in hypophysial stalk-transected beef heifers

Hypothalamic regulation of luteinizing hormone (LH) secretion and ovarian function were investigated in beef heifers by infusing LH-releasing hormone (LHRH) in a pulsatile manner (1 microgram/ml; 1 ml during 1 min every h) into the external jugular vein of 10 hypophysial stalk-transected (HST) animals. The heifers were HST approximately 30 mo earlier. All heifers had increased ovarian size during the LHRH infusion. The maximum ovarian size (16 +/- 2.7 cm3) was greater (P less than 0.01) than the initial ovarian size (8 +/- 1.4 cm3). Ovarian follicular growth occurred in 4 of 10 HST heifers in response to pulsatile LHRH infusion. In 2 heifers, an ovarian follicle developed to preovulatory size, but ovulation occurred in only 1 animal after the frequency of LHRH was increased (1 microgram every 20 min during 8 h). In blood samples obtained at 20-min intervals every 5th day, LH concentrations in peripheral serum remained consistently low (0.9 ng/ml) and nonepisodic in the 10 HST heifers during infusion of vehicle on the day before beginning LHRH. In 7 of 10 HST animals, episodic LH secretion occurred in response to pulsatile infusion of LHRH. In 3 of these long-term HST heifers, however, serum LH remained at basal levels and the isolated pituitary seemingly was unresponsive to pulsatile infusion of LHRH as indicated by sequential patterns of gonadotropin secretion obtained at 5-day intervals. These results indicate that pulsatile infusion of LHRH induces LH release in HST beef heifers.     

Neuroendocrine control of gonadotropin secretion

Luteinizing hormone releasing hormone (LHRH), a hypothalmic peptide that is concentrated in granules of neurons, has the capacity to release gonadotropins (luteinizing hormone (LH) and follicle stimulating hormone) from the pituitary gland. LHRH has been found in hypophysial portal blood of rats, monkeys, and rabbits. Antibodies to LHRH depress plasma LH concentrations in castrated animals and evoke testicular atrophy, but passive immunization against LHRH does not block the LH surge induced by estrogen in monkeys. Estrogens, progestin, prolactin, and dopamine have marked effects on LH secretion, yet an association between these effects and altered hypophysial portal blood concentrations of LHRH is not established. In view of the paucity of evidence demonstrating such a cause and effect relationship, two alternative proposals have become tenable. One, hormones and neurotransmitters may not alter the levels of portal blood LHRH, but rather alter the frequency of pulsatile LHRH secretion. Two, hormones, such as estrogens, progesterone, and prolactin, may alter the responsiveness of the gonadotropin-secreting cells to LHRH by affecting the secretion of dopamine.     

Prostaglandin D2 stimulates vasoactive intestinal polypeptide release into rat hypophysial portal blood

The effect of prostaglandin D2 (PGD2) on vasoactive intestinal polypeptide (VIP) release from the hypothalamus was examined by determining plasma VIP levels in rat hypophysial portal blood. Intraventricular injection of PGD2 (5 micrograms/rat) caused a 3-fold increase in the concentration of plasma VIP in hypophysial portal blood in anesthetized rats. A PGD2 metabolite, 13,14-dihydro-15-keto PGD2, did not affect VIP levels in portal blood. The flow rate of hypophysial portal blood was not changed after the injection of PGD2. The intraventricular injection of PGD2, but not PGD2 metabolite, resulted in an increase in peripheral plasma prolactin (PRL) levels in the rat. These findings suggest that PGD2 plays a stimulatory role in regulating VIP release from the hypothalamus into hypophysial portal blood and causes PRL secretion from the pituitary in rats.     

Negative feedback effects of chlormadinone acetate and ethynylestradiol on gonadotropin secretion in patients with prostatic cancer and male rats

Serum LH and FSH levels were determined before and after LH-RH injection (100 micrograms, i.m.) in patients with prostatic cancer who were chronically treated with either chlormadinone acetate (CMA, 100 mg/day) or ethynylestradiol (EE, 1 mg/day). In patients treated with EE, the levels of serum LH and FSH before and after injection of LH-RH were significantly lower than those in controls. On the other hand in patients treated with CMA, the basal levels of serum gonadotropins did not differ from those in controls, and the increase in gonadotropin after LH-RH injection was comparable to that in controls. To examine the effects of these steroids on the hypothalamo-hypophysial axis in the regulation of gonadotropin secretion, CMA or EE was implanted in castrated male rats. CMA, EE or cholesterol (control) was implanted in the hypothalamic median eminence-arcuate nucleus region through a stainless doublecannula. EE implantation resulted in a 75% decrease in serum LH (p < 0.001) and a 38% decrease in serum FSH (p < 0.05) from the control levels on day 5 of implantation. On the other hand, CMA implantation induced a 33% decrease in serum LH (p < 0.05) from the control level on day 3 of implantation, but no significant change in serum FSH levels. The injection of 2 micrograms/kg of LH-RH on day 7 of implantation induced significant lowering of LH and FSH levels. There was no significant difference between serum levels of the hormones 20 min after LH-RH injection for these two groups and those for the control group. These studies suggest that EE has a potent negative feedback effect on both LH and FSH secretion, and that CMA has a mild negative feedback effect on LH secretion.     

Oxytocin inhibits ACTH and peripheral catecholamine secretion in the urethane-anesthetized rat

Oxytocin (OT) generally has a stimulatory effect on ACTH secretion both in vitro and in vivo. As part of a study of ACTH-releasing factors in hypophysial portal blood, the effects of i.v. OT administration on plasma ACTH levels were tested in urethane-anesthetized rats. Surprisingly, i.v. injection of 10 micrograms OT lowered plasma ACTH levels by about 35% (P less than 0.01). It was reasoned that this paradoxical inhibition of ACTH secretion by OT might be mediated by inhibition of the unusually high rate of peripheral catecholamine secretion in this model. Measurement of plasma catecholamines before and after i.v. administration of 10 micrograms OT revealed a 53% inhibition of EPI (P less than 0.01) and 43% inhibition of NE (P less than 0.05). Administration of the beta-adrenergic antagonist propranolol (400 micrograms) 15 min before the beginning of the experiment completely blocked the inhibitory effects of OT on ACTH secretion and in fact unmasked the stimulatory effects of OT normally seen in conscious animals and in vitro. Superfused bisected adrenal glands exposed to 10(-6) M OT for 10 min secreted more than 30% less EPI and NE than control adrenals suggesting that the inhibition of EPI and NE secretion by OT in vivo occurs, at least in part, directly at the level of the adrenal. The data support the hypothesis that peripheral catecholamines may at times be directly involved in the control of ACTH secretion and also suggest that OT, which has recently been identified in the adrenal medulla, may have important paracrine functions in the regulation of adrenal catecholamine secretion.     

Site of negative feedback action of estrogen on gonadotropin secretion in normal women

We have reported that iv administration of conjugated estrogens results in no significant change in the plasma LH-RH level during the negative feedback phase of LH, suggesting that estrogen does not suppress LH by decreasing hypothalamic LH-RH. To determine the site of estrogen action during the negative feedback phase, we studied the pituitary response to a small amount of LH-RH after estrogen administration in normal cyclic women in the mid-follicular phase. The pituitary responses to an iv bolus of 2.5 micrograms of synthetic LH-RH were evaluated by measuring serum LH and FSH 2 h before and 8 h after administration of 20 mg of conjugated estrogens (Premarin). The mean levels of serum LH and FSH were significantly (p less than 0.05) decreased 8 h after the injection. The peak responses of LH and FSH to LH-RH were also significantly (p less than 0.05) reduced after Premarin administration. These findings suggest that the negative feedback effect of estrogen on gonadotropin secretion is caused by its direct suppression on the pituitary response to LH-RH.     

Progesterone and LH variations after LH-RH administration in the luteal phase of the menstrual cycle

We have investigated the pituitary and luteal responses to LH-RH and their related changes. 11 normal women were studied during the luteal phase (day +4/+11). Blood samples were collected every 15 min for a basal period of 180 and 120 min after the intravenous administration of 25 micrograms of LH-RH. Progesterone (P) and LH were assayed by radioimmunoassay. Data were analyzed as maximum peak and its percent increase (delta max), integrated secretory area (ISA) and percent increase of ISA (delta A) in respect to basal values for both P and LH. LH-RH elicited a secretory response of both hormones in all cases. ISA of LH was significantly greater after LH-RH administration in respect to basal values (p less than 0.001) and delta max accounted to 475 +/- (SE) 36% of the basal concentration. Luteal responsiveness varied from about 115-130% to more marked increments. ISA of P differed from basal to stimulated conditions (p less than 0.05) and delta max was 166 +/- (SE) 14%. The analysis of temporal relationship between P and LH secretion showed that LH promptly rose after LH-RH, while the enhancement of P plasma levels occurred within 31 +/- 19 min after LH rise. Then P levels reached a plateau, values of which were statistically different from those observed before LH-RH administration. In two cases where luteal function was blunted or absent, in spite of marked increments of LH, P secretion did not occur. These data are consistent with the presence of close relationships between hypothalamic, pituitary and luteal functions and strengthen the contention about the usefulness of LH-RH during luteal phase for the lifespan and maintenance of corpus luteum.     

The role of protein kinase C in LH release

To investigate the postreceptor mechanism, especially the role of protein kinase C (C-kinase), in luteinizing hormone (LH) release from anterior pituitary cells, dispersed rat anterior pituitary cells were stimulated with luteinizing hormone-releasing hormone (LH-RH), [D-Ser(tBu)]6 des-Gly-NH2(10) ethylamide (Buserelin), 12-0-tetradecanoyl phorbol-13-acetate (TPA) and trifluoperazine (TFP) and the LH released into the medium was determined by radioimmunoassay. LH released by combined stimulation with TPA and either LH-RH or Buserelin was significantly less than that released by LH-RH or Buserelin alone (LH-RH: p less than 0.05; Buserelin: p less than 0.01). It is thought that this paradoxical phenomenon occurred due to desensitization accompanied by down-regulation of LH-RH receptors induced by TPA. This hypothesis was supported by the finding indicating that the binding capacity of LH-RH receptors decreased in a time-course manner during incubation with TPA. The amount of LH released by combined stimulation with TPA and TFP was significantly greater than with TPA alone (P less than 0.01). This suggests that TFP has dual actions, i.e., facilitating and inhibiting LH release.     

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.     

Pulsatile infusion of luteinizing hormone-releasing hormone: Effects on luteinizing hormone secretion and ovarian function in prepuberal gilts

Ten intact and hypophysial stalk-transected (HST), prepuberal Yorkshire gilts, 112–160 days old, were subjected to a pulsatile infusion regimen of luteinizing hormone-releasing hormone (LHRH) to investigate secretion profiles of luteinizing hormone (LH) and ovarian function. A catheter was implanted in a common carotid artery and connected to an infusion pump and recycling timer, whereas an indwelling external jugular catheter allowed collection of sequential blood samples for radioimmunoassay of LH and progesterone. In a dose response study, intracarotid injection of 5 μg LHRH induced peak LH release (5.9 ± 0.65 ng/ml; mean ± SE) within 20 min, which was greater (P < 0.001) than during the preinjection period (0.7 ± 0.65 ng/ml). After HST, 5 μg LHRH elicited LH release in only one of three prepuberal gilts. Four intact animals were infused with 5 μg LHRH (in 0.1% gel phosphate buffer saline, PBS) in 0.5-ml pulses (0.1 ml/min) at 1.5-h intervals continuously during 12 days. Daily blood samples were obtained at 20-min intervals 1 h before and 5, 10, 20, 40, 60 and 80 min after one LHRH infusion. Plasma LH release occurred in response to pulsatile LHRH infusion during the 12-day period; circulating LH during 60 min before onset of LHRH infusion was 0.7 ± 0.16 ng/ml compared with 1.3 ± 0.16 ng/ml during 60 min after onset of infusion (P < 0.001). Only one of four intact gilts ovulated, however, in response to LHRH infusion. This animal was 159 days old, and successive estrous cycles did not recur after LHRH infusion was discontinued. Puberal estrus occurred at 252 ± 7 days in these gilts and was confirmed by plasma progesterone levels. These results indicate that intracarotid infusion of 5 μg LHRH elicits LH release in the intact prepuberal gilt, but this dosage is insufficient to cause a consistent response after HST.     

Plasma immunoreactive somatostatin levels in rat hypophysial portal blood: Effect of glucagon administration

Plasma somatostatin levels of the hypophysial portal blood was examined in urethane-anesthetized rats. Portal blood was withdrawn at a rate of 4.7 μl/min via a cannula placed over the stump of the pituitary stalk, collected into the ice-cold tube at 20min intervals before and after the intraventricular injection of test materials. Immunoreactive somatostatin extracted from the plasma with acid acetone was measured by a specific radioimmunoassay.Basal plasma somatostatin concentrations, 778±52pg/ml (means±SE), did not significantly change after the administration of control solution (0.1N acetic acid in physiological saline), while intraventricular injection of glucagon (2, 10 and 50 μg) caused a significant and dose-related increase in plasma somatostatin during the first 20min.These results suggested that somatostatin release from the median eminence into the hypophysial portal vessel was stimulated by glucagon, although the physiologycal significance remains to be clarified.     

Naloxone evokes large-amplitude GnRH pulses in luteal-phase ewes

Ewes were sampled during the mid-late luteal phase of the oestrous cycle. Hypophysial portal and jugular venous blood samples were collected at 5-10 min intervals for a minimum of 3 h, before i.v. infusions of saline (12 ml/h; N = 6) or naloxone (40 mg/h; N = 6) for 2 h. During the 2-h saline infusion 2/6 sheep exhibited a GnRH/LH pulse; 3/6 saline infused ewes did not show a pulse during the 6-8-h portal blood sampling period. In contrast, large amplitude GnRH/LH pulses were observed during naloxone treatment in 5/6 ewes. The mean (+/- s.e.m.) amplitude of the LH secretory episodes during the naloxone infusion (1.07 +/- 0.11 ng/ml) was significantly (P less than 0.05) greater than that before the infusion in the same sheep (0.54 +/- 0.15 ng/ml). Naloxone significantly (P less than 0.005) increased the mean GnRH pulse amplitude in the 5/6 responding ewes from a pre-infusion value of 0.99 +/- 0.22 pg/min to 4.39 +/- 1.10 pg/min during infusion. This episodic GnRH secretory rate during naloxone treatment was also significantly (P less than 0.05) greater than in the saline-infused sheep (1.53 +/- 0.28 pg/min). Plasma FSH and prolactin concentrations did not change in response to the opiate antagonist. Perturbation of the endogenous opioid peptide system in the ewe by naloxone therefore increases the secretion of hypothalamic GnRH into the hypophysial portal vasculature. The response is characterized by a large-amplitude GnRH pulse which, in turn, causes a large-amplitude pulse of LH to be released by the pituitary gland.     

The effects of gastric inhibitory polypeptide (GIP) on the release of anterior pituitary hormones

Several members of the secretin family of hormones have been demonstrated to alter anterior pituitary hormone secretion. Here we report the action of gastric inhibitory polypeptide (GIP) on gonadotropin and somatotropin release. Intraventricular injection of 1 microgram (0.2 nmole) GIP (2.5 microliters) produced a significant decrease in plasma FSH at 30 (p less than 0.02) and 60 min after its injection (p less than 0.01). The FSH-lowering effect of a higher dose of 5 micrograms (1 nmole) of GIP was already developed at 15 min (p less than 0.01) and was prolonged until the end of the experiment (60 min, p less than 0.05). No change in plasma LH was detected at any time during the experimental period. If 5 micrograms of estradiol-benzoate were given SC 48 hr prior to experiment, the initial values of FSH and LH were markedly decreased. In these animals GIP failed to influence plasma FSH and LH. When dispersed anterior pituitary cells from OVX rats were cultured overnight and incubated in vitro with GIP, the peptide was found to induce both FSH and LH release. Highly significant release occurred with the lowest dose tested of 10(-7) M and there was a dose-response effect for both hormones. The slope of the dose-response curve was similar for both FSH and LH release. GIP was less potent than LHRH which produced a greater stimulation of both FSH and LH release at a dose of 10(-9) M than did 10(-7) M GIP. The two peptides had an additive effect on the release of both FSH and LH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulsatile nature of luteinizing hormone release is maintained during luteinizing hormone-releasing hormone stimulation in normal male rats

The plasma LH concentration is believed to be reasonably steady in normal male rats. We found that LH is released in a regular pulsatile fashion. The overall mean concentration of plasma LH in normal male rats was 46.6 +/- 4.4 (mean +/- SEM) ng/ml. The normal male rats showed periodic LH pulses: the mean pulse amplitude was 144.4 +/- 25.5 ng/ml and the inter-peak interval was 22.5 +/- 2.0 min. Each pulse lasted 9.7 +/- 0.8 min. When LH-RH (1 microgram/kg) was injected as a bolus, the peak concentration was attained in 10-30 min reaching a peak concentration of 279.4 +/- 39.6 ng/ml. Distinct pulsatile bursts of plasma LH were discernible during the period of elevated plasma LH concentration. When a higher dose of LH-RH (5 micrograms/kg) was administered, the LH concentration slowly increased to a peak concentration of 400.2 +/- 38.7 ng/ml in 20-40 min. The pulsatile nature of the LH concentration was recognizable with distinct bursts. We have observed that: (a) normal male rats release LH in a pulsatile fashion with an approximate 20-min inter-peak interval; (b) mean LH pulses last less than 10 min, and (c) the LH pulses are visible even with elevated LH and LH-RH concentrations in the general circulation.     

Inhibitory control of the pituitary LH secretion by LH-RH in male rats.

Luteinizing hormone-releasing hormone (LH-RH) was administered to prepubertal male rats (intact, castrate or castrate-adrenalectomized, 60 g body weight) for 28 days (1 microgram LH-RH/day, s.c.), at a 10-fold physiological dose, as compared to the minimal FSH-releasing dose of 100 ng/rat s.c. In intact rats, serum LH and weight of androgen-dependent organs (vented prostate, seminal vesicles) were reduced after 14 days of treatment. In castrate rats, the postcastration rise in serum LH was abolished by treatment. Pituitary LH content, FSH secretion and prolactin secretion were not suppressed. Hypothalamic LH-RH was increased at 14 and 21 days. In castrate adrenalectomized male rats, LH secretion was also suppressed by 1 microgram LH-RH s.c. x 28 days. The hypothalamic LH-RH content did not increase. The pituitary LH-RH receptor level was not down-regulated after 14 days treatment either in intact or castrate male rats. Pituitary inhibition (LH release) in rats by a supraphysiological dose of LH-RH given for 28 days indicates that the optimal regime for chronic treatment has to be determined by monitoring LH release at regular intervals. Direct pituitary inhibition by LH-RH may explain some of the unexpected antifertility effects observed with high doses of LH-RH.     

Effects of gonadal steroids on follicle-stimulating hormone and luteinizing hormone secretion by pituitary cells from castrated and intact male rats

The effectiveness of androgens in suppressing gonadotropin secretion declines with time following orchidectomy; however, the mechanism for this acquired resistance to androgen action is unknown. The role of the pituitary was studied by use of perifused rat pituitary cells and cells in monolayer culture. Pituitary cells from 7-wk-old intact male rats and rats that had been castrated 2 wk previously were treated with 10 nM testosterone (T) for 24 h; cells were then packed into perifusion chambers and stimulated with 2.5 nM GnRH for 2 min every hour for 8 h during which time T treatment was continued. T suppressed GnRH-stimulated LH secretion and LH pulse amplitude equally in both groups to approximately 60% of control values. Interpulse LH secretion was unchanged by T in either group. GnRH-stimulated FSH release was suppressed more (p less than 0.05) by T with cells from castrated rats than with cells from intact rats (76 +/- 4% vs. 90 +/- 2% of control; mean +/- SEM). By contrast, the action of T to increase interpulse basal FSH secretion was less (p less than 0.05) with cells from castrated rats (115 +/- 10% of control) than with cells from intact rats (146 +/- 6% of control). T treatment for 72 h also increased basal FSH secretion by pituitary cells in monolayer culture to a lesser extent with cells from castrated rats than with cells from intact rats (151 +/- 14% vs. 191 +/- 16% of control, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct hypophysial inhibition of luteinizing hormone release by dopamine in the rabbit.

The role and site of action of dopamine in regulating gonadotropin secretion remain unclear. In the present study, we investigated the possibility that dopamine regulates LH secretion by acting directly on the pituitary gland of the rabbit. The effect of dopamine infusion on LHRH-evoked LH release was determined in intact and pituitary stalk sectioned animals. Intravenous injection of LHRH (1 μg) in intact and acutely stalk sectioned rabbits increased peripheral plasma LH levels from a resting value of 0.2 ng/ml to maximal values of 12–14 ng/ml within 10–20 min. When dopamine was infused iv at a dose of 6.6 μg/min/kg BW from 30 min before LHRH injection until 120 min after, the rise in plasma LH levels in intact and stalk sectioned animals was decreased by 50–70%. However, dopamine infused at a lower dose (0.66 μg/min/kg BW) or at a higher dose (66.0 μg/min/kg BW), did not affect the LHRH-induced secretion of LH. These results suggest that dopamine can exert a direct hypophysial inhibitory effect on release of LH. They also demonstrate that dopamine is inhibitory only within a restricted dose-range, extending to the pituitary an established property of dopamine in the cardiovascular system.     

Feedback control of FSH secretion in the male rat

Site of feedback control of FSH secretion in the male rat was studied by measuring changes in serum LH, FSH and hypothalamic LH-RH by radioimmunoassay in rats after castration and after 500 rad X-irradiation to the testis. The rise in serum LH and FSH in castrated animals was associated with a significant fall in hypothalamic LH-RH 16 and 24 days after castration. Serum FSH rose significantly after X-irradiation without a significant change in serum LH or hypothalamic LH-RH content up to 30 days after irradiation. When pituitary halves from X-irradiated animals were incubated in vitro in the presence or absence of synthetic LH-RH, there was a significant rise in FSH (but not LH) released in the incubation medium in the absence of added LH-RH. The response of the pituitaries to LH-RH was, however, not different between control and irradiated rats. It is concluded that the testicular FSH-inhibitory substance acts predominantly at the pituitary gland on the LH-RH independent release of FSH.