High PRL Levels Research Articles

Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats.

Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.

Macroprolactinomas and functionless pituitary tumours

Abstract. In 32 patients with macroprolactinomas or functionless pituitary macroadenomas biochemical and clinical data were correlated with PRL immunocytochemistry. Serum PRL levels revealed a positive correlation with tumour PRL content. Hyperprolactinaemia of 3000 mU/l or more was found only in patients with PRL-positive tumours. In 15 patients with borderline hyperprolactinaemia (below 3000 mU/l), 7 PRL-positive and 8 PRL-negative macroadenomas were found, and in 9 normoprolactinaemic patients 4 PRL-positive and 5 PRL-negative macroadenomas. Patients with PRL-immunostainable tumours had significantly higher median basal serum PRL (P ≤ 0.05) than patients with PRL-negative tumours. PRL stimulation after TRH, basal and GnRH-stimulated FSH and LH did not show significant differences between the two groups. A discriminant analysis using 6 biochemical variables was attempted to differentiate between PRL-negative and -positive tumours, which would be helpful in patients with borderline hyperprolactinaemia. Dopamine agonist therapy led to suppression of serum PRL with few exceptions in patients with PRL-positive and -negative tumours, whereas shrinkage was only observed in PRL-immunostainable tumours with high serum PRL levels (over 18 000 mU/l). All patients with PRL-negative tumours showed no change or even growth of the tumour despite dopamine agonist therapy. Our observations indicate that a pituitary macroadenoma associated with serum PRL of more than 3000 mU/l is most probably a prolactinoma (tumour immunostainable for PRL). Dopamine agonist therapy is effective in PRL suppression and tumour shrinkage in most of these patients. Macroadenomas without hormone hypersecretion or with borderline hyperprolactinaemia below 3000 mU/l may or may not contain PRL-immunostainable cells. Dopamine agonist therapy is effective in suppression of serum PRL also in most of these patients, but definite tumour shrinkage was not observed even in patients with PRL-immunostainable tumours of this group.

D-Trp6-luteinizing hormone-releasing hormone inhibits sulpiride-induced hyperprolactinemia in normal men.

The effect of a potent agonistic analog of LHRH, D-Trp6-LHRH, on hyperprolactinemia induced by sulpiride was studied in normal men. Six men received sulpiride (100 mg, twice daily, orally) for 44 days. D-Trp6-LHRH was given sc during the last 2 weeks of sulpiride administration; the dose was 500 micrograms on the first day and 100 micrograms daily for the subsequent 14 days. All men had high serum PRL levels before D-Trp6-LHRH administration (mean +/- SEM, 56 +/- 9 ng/mL), which decreased significantly after the first dose of the analog (45 +/- 5 ng/mL; P = 0.031) and also after 15 days of analog administration (41 +/- 6 ng/mL; P = 0.016). These data demonstrate that administration of LHRH agonist can inhibit the hyperprolactinemic effect of sulpiride, suggesting a direct action of the analog on the pituitary gland to modulate PRL secretion.

Coordinated receptor regulation in ovarian granulosa cells.

The concept of receptor down regulation by its own hormone through internalization of the hormone-receptor complex is well established (for reviews, see Blecher and Bar, 1981; Kaplan, 1981). However, the cellular basis for heterologous receptor regulation is less well defined. The process is important in endocrine cells, particularly in the ovarian cell, because granulosa and luteal cells are under the control of at least a dozen different hormones and growth factors (Hseuh et al., 1984). To further complicate matters, any one of these agents may positively or negatively regulate receptors for other hormones. For example, physiologic levels of LH increase prolactin (Prl) receptor number, while pharmacologic levels of LH induce a transient decrease of Prl receptors (Chen et al., 1979). Likewise, physiologic levels of Prl result in an increase of LH receptors in these cell types (Richards, 1979), but the effect of high levels of Prl on LH receptor has not been well studied.KeywordsGranulosa CellLuteal CellOvarian Granulosa CellGranulosa Cell CultureSteroidogenic ResponseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Prolactin in severe toxemia of pregnancy

Plasma PRL levels were measured in 111 normal pregnant women and in 21 patients with severe toxemia of pregnancy. Twelve of 21 patients with severe toxemia of pregnancy showed high PRL levels in zone A (greater than mean value + 1 S.D. of PRL values in normal pregnancy). These 12 were significantly lower (P less than 0.02) in the Ccre rate, at 70.2 +/- 19.2 ml/min, than 5 toxemia patients (101.4 +/- 26.7 ml/min) in zone B (mean + 1 S.D. approximately mean) and 4 toxemia patients (110.0 +/- 35.3 ml/ml) in zone C (mean approximately mean -1 S.D.). Also, BUN, proteinuria and uric acid levels in zone A patients were higher than in those in zone B and C. However, no correlation was found between PRL levels and mean diastolic and systolic blood pressure. These results suggest that high PRL concentrations in toxemia of pregnancy may be associated with renal dysfunction.

The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue SMS 201-995 in patients with prolactinomas and acromegaly.

The somatostatin analogue SMS 201-995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201-995 and whether co-secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201-995. The s.c. administration of 50 micrograms SMS 201-995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 micrograms three times a day also did not affect PRL levels. The single administration of 50 micrograms SMS 201-995 in 22 acromegalic patients lowered plasma GH levels for 2-6 h to less than 5 micrograms/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH-containing tumours and in seven patients there were mixed GH/PRL-containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201-995 did not differ between the patients with pure GH or mixed GH/PRL-containing adenomas. Plasma PRL levels were not affected by SMS 201-995 in the patients with pure GH-secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL-containing tumour with SMS 201-995 (100 micrograms three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201-995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL-containing tumours PRL secretion in some patients is sensitive to SMS 201-995, making these patients good candidates for chronic treatment with the analogue. The simultaneous presence of PRL in the GH-secreting pituitary tumour or the presence of hyperprolactinaemia in acromegalics does not play a role in the sensitivity of GH secretion to the somatostatin analogue.

Further acquisitions on gonadal function in bromocriptine treated hyperprolactinemic male patients

The diurnal variation of plasma total and free testosterone (tT and fT) and the gonadotropinemic response to LH-RH were evaluated in a group of hyperprolactinemic impotent males with pituitary microprolactinoma before and during therapy with bromocriptine, a well known dopamine agonist drug. Before treatment, basal levels not only of tT but also of fT were decreased and the diurnal variation of both tT and fT was absent. Moreover, the LH-RH test showed a delay in the LH response peak, together with normal basal levels of LH. Bromocriptine therapy caused normalization of both the secretion response of LH to LH-RH and of the secretion pattern of tT and of fT (basal levels and diurnal variation) besides a significant decrease in PRL levels and an improvement in sexual function. The possible effects of high plasma levels of PRL at various levels of the hypothalamus-pituitary-testicular axis are discussed.

Seasonal changes in prolactin and luteinizing hormone in the polyandrous spotted sandpiper, Actitis macularia

The polyandrous spotted sandpiper (Actitis macularia) is a species characterized by female dominance over males and predominant male parental care. Prolactin (Prl) and luteinizing hormone (LH) were analyzed in plasma samples obtained serially from individuals across different stages of the breeding season. The reproductive status of each sampled individual was known in detail. Similar Prl values were obtained independently by two different assays. Males tended to have higher plasma Prl levels than females throughout the breeding season. Prl was significantly elevated in both sexes by the first few days of incubation. This rapid rise in Prl may indicate its role in brood patch development and the onset of incubation behavior. In males Prl continued to rise during incubation, whereas it remained constant in females. Higher levels of Prl in males than females, especially late in incubation, reflects the greater contribution of males to incubation. LH declined markedly in males and females from prelaying to early incubation. There was a significant negative correlation between Prl and LH among males, especially from the prelaying to early incubation phases of the season. There was no such correlation among females.

Hyperprolactinemia attenuates ovarian steroid stimulation of region-specific hypothalamic serotonin synthesis and luteinizing hormone release in ovariectomized rats.

Hyperprolactinemia adversely affects reproductive functions, presumably through an effect at the hypothalamic level. Given the numerous published reports linking hypothalamic serotonin (5-hydroxytryptamine, 5HT) mechanisms to the regulation of gonadotrophin secretion, we sought to determine the effects of experimentally induced hyperprolactinemia on ovarian steroid-induced increases in serum LH levels and region-specific hypothalamic 5HT synthesis in ovariectomized rats. In the first study, bilaterally ovariectomized Sprague-Dawley rats either received two pituitary homografts implanted beneath the left kidney capsule or were sham-grafted. Both groups of rats were injected subcutaneously with 5 micrograms/100 g of estradiol benzoate (E2) in corn oil vehicle at 08.00 h, 1 and 2 days before serum collection and 5 mg/100 g of progesterone (P) in corn oil vehicle at 07.00 h on the day of serum collection. Blood samples were collected via chronic indwelling jugular cannulae from each rat at 10.00, 12.00, 13.00, 14.00, 16.00 and 18.00 h. A statistically significant elevation in serum LH levels was detected at 13.00, 14.00 and 16.00 h. This increase in serum LH levels was significantly attenuated in rats bearing pituitary homografts, an effect attributed to the high serum PRL levels measured in these animals. In the second study, bilaterally ovariectomized Sprague-Dawley rats were divided into three experimental groups: (1) rats bearing two pituitary homografts and injected with E2 and P on the schedule and at the dosages previously described, (2) sham-grafted rats injected with E2 and P on the schedule and at dosages previously described and (3) sham-grafted rats injected with corn oil vehicle only.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin secretion in acromegalic patients before and after selective adenomectomy.

PRL secretion before and after transsphenoidal adenomectomy was studied in 13 patients with acromegaly. Six patient had elevated basal serum PRL levels before surgery, while 7 patients had normal levels. In every patient, the basal serum GH level decreased to less than 5.0 ng/ml after surgery. In the group (group A) with high basal serum PRL levels (mean +/- SD, 41.3 +/- 5.8 ng/ml) before surgery, the PRL levels decreased significantly (P less than 0.0002) to less than 10.0 ng/ml (4.8 +/- 3.6 ng/ml) after the operation. However, in the group (group B) with normal levels (10.8 +/- 4.4 ng/ml) before surgery, PRL levels changed little (7.8 +/- 3.1 ng/ml) after the operation. In group A, the increment of PRL after TRH injection decreased or disappeared (P less than 0.02; 4.1 +/- 2.4 ng/ml) after surgery compared with that before surgery (39.2 +/- 25.9 ng/ml). On the other hand, in group B, the increment of PRL after TRH injection was nearly unchanged (17.1 +/- 7.0 ng/ml) after surgery compared with that before surgery (19.3 +/- 8.0 ng/ml). The results indicate that PRL is secreted from the pituitary adenoma in acromegalic patients with hyperprolactinemia, while PRL secretion from the normal part of the pituitary gland is decreased.

Correlation between the number of thyroliberin binding sites, the tumour size and the plasma prolactin level in human prolactin-secreting adenomas.

Basal plasma prolactin (Prl) level, tumour size and [3H]thyroliberin (TRH) binding to tumour membranes were studied in 18 patients bearing Prl-secreting adenomas. Big tumours (grade III) were associated with high plasma Prl levels (median value: 1929 (range: 207-3570) ng/ml) and possessed numerous membrane TRH receptors (median value: 508 (range: 0-1200) fmol/mg of protein). By contrast, smaller tumours (grade II and I) were associated with lower plasma Prl levels (median values: 1085 (range: 40-1890) and 295 (range: 98-788) ng/ml, respectively) and possessed fewer membrane TRH receptors (median values 122 (range: 11-328) and 13 (range: 0-52) fmol/mg of protein, respectively). A direct positive correlation was demonstrated between the plasma Prl level and the number of [3H]TRH binding sites (rho: 0.729 P less than 0.001). That the higher number of TRH receptors is associated with the largest tumours may be of importance in hyperprolactinaemia and should be taken in account when speculating on the pathogenesis of human Prl-secreting adenomas.

Paradoxical suppression of prolactin secretion: involvement of catecholaminergic mechanisms and the adrenal gland.

Prolactin (Prl) secretion is normally elevated on the afternoon of pro-oestrus in the rat. Studies have shown that ether stress caused a 'paradoxical inhibiting effect' on these high Prl levels. The present study was designed to investigate whether the paradoxical suppression of Prl was mediated by the central nervous system or the adrenal glands. Plasma was obtained from adult female rats after sampling via intra-atrial catheters from 16.25-18.45 h on the afternoon of pro-oestrus. Restraint stress administered between 16.45-17.00 h induced the expected precipitous decrease in plasma Prl in intact animals. Pre-treatment of intact animals with the catecholamine receptor blocking agent haloperidol (1.0 mg/kg at 13.00 h) resulted in a further elevation of plasma Prl levels as compared with untreated controls, but eliminated the decrease of Prl in response to restraint stress. Although acutely adrenalectomized (ADX) animals proved to be highly sensitive to the bleeding procedures, initial Prl levels on the afternoon of pro-oestrus were not different from those of intact animals. Restraint stress under conditions of acute ADX was not found to induce the expected suppression of high Prl levels. Rather, the response was opposite to that which occurred in intact animals. These results indicate that the paradoxical suppression of Prl by restraint stress was mediated by catecholaminergic mechanisms, and that the adrenal gland was essential for the effect.

Gonadotropin and prolactin levels in follicular fluid of human ova successfully fertilized in vitro.

Follicular fluid (FF) and oocytes were obtained from 94 follicles of 36 women for fertilization in vitro. Ovulation was induced with human menopausal gonadotropin, and follicular aspiration was performed 36 h after an ovulatory injection of hCG. The concentrations of immunoreactive hCG, FSH, and PRL were correlated with the degree of maturation of the oocyte-corona-cumulus complex mass (OCCC), fertilization, rate of cleavage, and the incidence of pregnancy after embryo transfer. Immature OCCC were derived from follicles that contained significantly lower levels of FSH than those from which intermediate and mature OCCC were derived (5.2 +/- 0.6 vs. 11.1 +/- 1.2 mlU/ml; P less than 0.05). FF from oocytes that were successfully fertilized contained higher levels of both hCG and FSH than FF surrounding oocytes that did not fertilize (136.7 +/- 8.7 vs. 108.5 +/- 10.3 mlU/ml hCG; 10.55 +/- 0.6 vs. 5.3 +/- 0.8 mIU FSH, respectively). There was no correlation between early embryonic growth rate and FF concentrations of FSH, hCG, and PRL. Ova reaching the two-cell stage 40 h after fertilization in vitro were associated with the same FF concentrations of FSH, hCG, and PRL as those that cleaved to the four-cell stage. The PRL concentration in FF was significantly higher in mature fertilized ova and in fertilized ova that were associated with a successful pregnancy. It is suggested that the intrafollicular concentration of FSH is associated with the degree of mucification of the OCCC, but FF levels of both FSH and hCG are associated with successful fertilization. High levels of PRL in FF were associated with successful pregnancy and may imply a role of this hormone in oocyte maturation.

Examination of prolactin and pituitary-adrenal axis components as intervening variables in the adrenalectomy-induced inhibition of gonadotropin response to castration.

Adrenalectomy performed at the same time as, or 12 h after, castration delays the postcastration rise in LH and FSH for at least 12 h. We tested three mechanisms previously advanced as possible mediators in this suppression: 1) blocking PRL in castrate-adrenalectomized males with bromoergocryptine did not restore the normal postcastration rise in serum LH and FSH, eliminating high PRL levels as a cause of this gonadotropin suppression; 2) exogenous ACTH given at the time of orchidectomy did not inhibit either gonadotropin, eliminating high peripheral ACTH as an agent of adrenalectomy-induced suppression of LH and FSH; and 3) intestinal traction performed at the same time as orchidectomy suppressed the secretion of LH and FSH to the same degree as adrenalectomy, ruling out the lack of any adrenal factor as a means by which adrenalectomy blocked gonadotropin secretion. Our data suggest that the adrenalectomy-induced suppression of LH is due to a neurally mediated stress response probably resulting in suppression of GnRH secretion. In other treatment groups, we implanted cortisol before surgery to test the effect of ACTH suppression on LH and FSH secretion in castrate-adrenalectomized animals. A striking divergence between LH and FSH was seen in response to cortisol treatment. Cortisol suppressed LH, but not FSH, in castrate animals, and restored postcastration FSH, but not LH, secretion 12 h after combined castration-adrenalectomy. This divergence between LH and FSH secretion suggests that the effect of adrenalectomy on the two gonadotropins might result from different mechanisms. It is also possible that the differential effect of cortisol on LH and FSH secretion is not relevant to the effect of adrenalectomy on the postcastration secretion of these gonadotropins. These data add to the evidence, however, that LH and FSH are regulated by different mechanisms under many experimental conditions, including stress and elevated corticoid levels.

Stimulation of spermatogenesis in stalk-sectioned rhesus monkeys by testosterone alone.

Testosterone alone stimulated spermatogenesis in four adult, pituitary stalk-sectioned rhesus monkeys. Ten to 14 weeks after transection of the pituitary stalk, testicular volumes declined to about one fifth of the presurgical values. Serum LH levels declined precipitously, being undetectable 1 week postsurgery, and serum testosterone levels were indistinguishable from those of castrated male monkeys by the 5th week postsurgery. After a transient decline, serum PRL levels increased to high values in all four monkeys throughout the rest of the postsurgery period. Twelve weekly injections of 250 mg testosterone enanthate resulted in peak testosterone levels around 25-fold higher than presurgical levels. Estradiol levels increased about 4-fold over presurgical levels, and PRL also increased further during the treatment phase. Small ejaculates were produced by electrostimulation by the 5th week of treatment. Thereafter, the ejaculate weight increased. Sperm were found from the 10th week in all four monkeys. By the 13th week of treatment, sperm counts in three monkeys ranged from 17-60 X 10(6) sperm/ejaculate. The sperm counts continued to increase for the first 4 weeks after the cessation of the testosterone enanthate injections. Thereafter, the sperm counts declined, and all four animals produced azoospermic ejaculates between 10 and 31 weeks posttreatment. Moreover, testosterone levels declined slowly and nonuniformly among the four animals. Testicular volumes declined and were at the lowest levels 14 weeks posttreatment. Estradiol and PRL levels also declined posttreatment. It is concluded that testosterone alone can stimulate spermatogenesis in stalk-sectioned rhesus monkeys even in the face of high serum PRL and estradiol levels.

Increased sensitivity to the negative feedback effects of testosterone induced by hyperprolactinemia in the adult male rat.

High plasma levels of PRL induced by transplants of two donor pituitaries under the kidney capsule of adult male rats resulted in a prolonged suppression of plasma levels of LH and FSH although testosterone levels were maintained within normal limits. Castration of rats with pituitary transplants resulted in a normal though delayed rise in serum levels of both LH and FSH to levels equivalent to those in normal castrated controls. This increase in gonadotropin levels occurred in spite of maintenance of elevated PRL levels. Two experiments were carried out in which testosterone was restored after castration by Silastic testosterone-containing implants of various lengths (Exp 1:60, 30, and 10 mm; Exp 2: 30, 20, 10, 5, and 2 mm). In both experiments 60- and 30-mm testosterone implants prevented the postcastration rise in LH and FSH in both control and hyperprolactinemic rats. However, although the shorter testosterone implants delayed this rise in control rats, levels of LH and FSH increased by 4 days and were not significantly different from castrated rats without testosterone implants by 15 days after castration. In contrast, this rise in gonadotropins was abolished or considerably delayed by the shorter implants in hyperprolactinemic rats, demonstrating an increase in sensitivity of the hypothalamic pituitary axis to the negative feedback effects of testosterone in these animals. These results suggest that 1) to maintain suppression of gonadotropin secretion in hyperprolactinemia high levels of PRL alone are insufficient and gonadal steroids are required, and 2) high levels of PRL appear to sensitize the hypothalamic-pituitary axis to the negative feedback effects of gonadal steroids.

Climacteric symptoms, fat mass, and plasma concentrations of LH, FSH, Prl, oestradiol-17 beta and androstenedione in the early post-menopausal period.

Abstract. The relations between climacteric symptoms, fat mass, time after the menopause, and plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (Prl), oestradiol-17β, and androstenedione were studied in 313 normal females in their early post-menopausal period. The mean age of the women was 50 years (45–54 years, range) and the time elapsed since the last menstrual bleeding was 19.8 months (4–46 months). Most women had mild to moderate climacteric complaints. The participants were examined and filled in a questionnaire containing the 11 symptoms of Kupperman index. A total of 61% of the women complained of hot flushes and from 9% to 44% complained of the remaining 10 Kupperman symptoms. Women with hot flushes (n = 196) had a higher mean score (P < 0.01) of the remaining symptoms than women without (n = 117). Plasma concentrations of LH and FSH were significantly higher and levels of oestradiol-17β and androstenedione were significantly lower in women complaining of hot flushes than in women without. Plasma levels of FSH was significantly (P < 0.05) higher and levels of oestradiol17β was signficantly (P < 0.01) lower in women with insomnia than in women not complaining of this symptom and women with depression had significantly (P < 0.01) higher Prl levels than women without. The months since the menopause were related to plasma levels of FSH (r = +0.216, P < 0.01) and oestradiol-17β levels (r = −0.306, P < 0.001) but not to plasma concentration of LH, Prl and androstenedione. Fat mass was related to plasma FSH and androstenedione concentrations and correlation was found between oestradiol-17β and androstenedione (r = +0.334, P < 0.001). Surprisingly, no correlation between hot flushes and fat mass was found.

Anterior pituitary gland secretion after forebrain ablation: periovulatory gonadotropin release.

We sought to determine whether the estrous phase of FSH release in cyclic female rats is dependent on the immediate presence of the diencephalon. A piece of forebrain, the diencephalon and part of the telencephalon, was surgically removed from female rats between 1130--1300 or 2000-2200 h on proestrus. Blood was withdrawn through indwelling venous cannulae during the afternoon and evening of proestrus and the early morning of estrus for RIA of plasma LH, FSH, and PRL concentrations. In rats sham operated at either time period, plasma LH, FSH, and PRL levels rose from 1345 to 1800 h on proestrus. Whereas the plasma LH and PRL concentrations fell from 1800 h on proestrus to 0300 h on estrus, the plasma FSH concentrations remained elevated during this period. The removal of the piece of forebrain around noon on proestrus blocked the rises in the plasma LH and FSH levels and caused high plasma PRL concentrations from 1345 h on proestrus to 0300 h on estrus. The removal of the piece of forebrain during the evening of proestrus did not interfere with the fall in plasma LH concentrations or the maintenance of elevated plasma FSH concentrations during either late proestrus or the early morning estrus, but did cause high plasma PRL levels during that time interval. Hypophysectomy combined with removal of the forebrain piece during the evening of proestrus resulted in a drop in plasma FSH and PRL concentrations. The results confirm that in the rat, 1) the prosencephalon plays an acute stimulatory role n causing the preovulatory LH surge and the proestrous phase of FSH release, 2) the prosencephalon exerts effects during the afternoon and/or early evening of proestrus that cause the estrous phase of FSH release, and 3) the estrous phase of FSH release occurs in the absence of acute diencephalic stimulation.

Effects of a Prolactin- and Adrenocorticotropin-Secreting Tumor on Gonadotropin Levels and Accessory Sex Organ Weights in Adult Male Rats: A Possible Role of the Adrenals

The presence of the transplantable PRL- and ACTH-secreting tumor 7315a in intact male rats resulted in very high serum PRL levels, decreased levels of LH and FSH, and reduced weights of testes and accessory sex organs. In gonadectomized rats bearing a small testosterone-filled capsule, the tumor inhibited the postcastration rise in gonadotropins and reduced the weights of the prostate and seminal vesicles. However, after adrenalectomy of intact or gonadectomized male rats bearing a small testosterone-filled capsule, inhibitory effects of the tumor on serum gonadotropin levels or on reproductive organ weights were totally absent. These results show that in adrenalectomized male rats hyperprolactinemia in itself doses not affect gonadotropin secretion and the androgenic action of testosterone. Rather, the tumor might exert a gonadotropin inhibitory action through elevated levels of PRL combined with progesterone, which is secreted by the ACTH-stimulated adrenal.

Specific cells of human amnion selectively localize prolactin.

The presence of PRL in high concentration in human amniotic fluid has been related to changes in water transport across amnion but not chorion leave. The cellular composition of human amniotic epithelium has been reported to include at least two structurally distinct cell types, known as light cells and dark cells, that differ in their ability to transport large molecules. In the present study, human amnion obtained from term cesarean section was evaluated through the use of autoradiography as to its ability to localize hormones of similar and variant molecular sizes. Amniotic epithelium exposed to [125I]human PRL, [125I]human Gh, [125I]human beta-endorphin, [125I]bovine FSH, and sodium 125I alone was found to display a selectivity in its ability to localize [125I]human PRL only. Furthermore, the selective localization of [125I]human PRL was found to be specific to the light cells, because dark cells failed to localize any of the other tracers used. These data provide additional evidence in support of the recently proposed concept that term human amniotic epithelium consists of at least two functionally distinct cell types. Furthermore, the high levels of PRL in amniotic fluid may have a specific physiologic role in the amniotic membrane during human gestation.