Effects of cranial cervical ganglionectomy and castration of male lambs. II. 24 hour plasma profiles of luteinizing hormone, testosterone and prolactin

Male lambs were utilized in an experiment designed to evaluate the effects of cranial cervical ganglionectomy (GX), castration and age on hormone secretion profiles. Blood plasma samples were collected at hourly intervals for 24 hours from 24 lambs aged 101 days and 20 lambs aged 277 days, then assayed for concentrations of luteinizing hormone (LH), testosterone and prolactin. At both ages pulsatile secretion of LH and testosterone was confirmed, but no circadian rhythm of LH testosterone or prolactin secretion was detected. Castration elevated LH levels significantly at both ages. GX and its interaction with castration had no effect on LH secretion at 101 days, but at 277 days these factors were significant, largely due to elevated levels being recorded from GX castrates. GX did not affect testosterone levels in entire animals at either age, while plasma from castrates contained no detectable testosterone. GX reduced prolactin concentrations at 101 days of age (summer) but elevated them at 277 days of age (winter). Castration and the interaction of castration with GX had no significant influence on plasma prolactin levels at either age. This study confirmed that the pineal gland of sheep is involved in the regulation of prolactin secretion, and probably influences LH secretion as well.     

Effects of the dopamine agonist cabergoline on the pulsatile and TRH-induced secretion of prolactin, LH, and testosterone in male beagle dogs

In the present study, the pulsatile serum profiles of prolactin, LH and testosterone were investigated in eight clinically healthy fertile male beagles of one to six years of age. Serum hormone concentrations were determined in blood samples collected at 15 min intervals over a period of 6 h before (control) and six days before the end of a four weeks treatment with the dopamine agonist cabergoline (5 microg kg(-1) bodyweight/day). In addition, the effect of cabergoline administration was investigated on thyrotropin-releasing hormone (TRH)-induced changes in the serum concentrations of these hormones. In all eight dogs, the serum prolactin concentrations (mean 3.0 +/- 0.3 ng ml(-1)) were on a relatively constant level not showing any pulsatility, while the secretion patterns of LH and testosterone were characterised by several hormone pulses. Cabergoline administration caused a minor but significant reduction of the mean prolactin concentration (2.9 +/- 0.2 ng ml(-1), p < 0.05) and did not affect the secretion of LH (mean 4.6 +/- 1.3 ng ml(-1) versus 4.4 +/- 1.7 ng ml(-1)) or testosterone (2.5 +/- 0.9 ng ml(-1) versus 2.4 +/- 1.2 ng ml(-1)). Under control conditions, a significant prolactin release was induced by intravenous TRH administration (before TRH: 3.8 +/- 0.9 ng ml(-1), 20 min after TRH: 9.1 +/- 5.9 ng ml(-1)) demonstrating the role of TRH as potent prolactin releasing factor. This prolactin increase was almost completely suppressed under cabergoline medication (before TRH: 3.0 +/- 0.2 ng ml(-1), 20 min after TRH: 3.3 +/- 0.5 ng ml(-1)). The concentrations of LH and testosterone were not affected by TRH administration. The results of these studies suggest that dopamine agonists mainly affect suprabasal secretion of prolactin in the dog.     

Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse

Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is controlled by circulating testosterone. Exactly how androgens exert their feedback control of gonadotrophin secretion (and whether this is at the level of the pituitary), as well as the role of AR in other pituitary cell types remains unclear. To investigate these questions, we exploited a transgenic mouse line (Foxg1^Cre/+; AR^fl/y) which lacks androgen receptor in the pituitary gland. Both circulating testosterone and gonadotrophins are unchanged in adulthood, demonstrating that AR signalling is dispensable in the male mouse pituitary for testosterone-dependent regulation of LH secretion. In contrast, Foxg1^Cre/+; AR^fl/y males have a significant increase in circulating prolactin, suggesting that, rather than controlling gonadotrophins, AR-signalling in the pituitary acts to suppress aberrant prolactin production in males.     

The effect of dexamethasone on TSH and prolactin secretion after TRH stimulation

Serum thyrotropin (TSH) and prolactin levels were measured after intravenous administration of 400 μg of synthetic thyrotropin-releasing hormone (TRH) in 13 normal subjects and six hypothyroid patients before and after three days of administration of dexamethasone 2 mg per day. In the normal subjects dexamethasone suppressed baseline serum levels and secretion of TSH after TRH stimulation. On the other hand, it had no effect on the hypothyroid patients. In the control group dexamethasone also suppressed baseline serum levels but not secretion of prolactin after TRH stimulation. Dexamethasone had no effect on prolactin levels in the hypothyroid group. It is concluded that in normal patients short-term administration of dexamethasone has an inhibitory effect on TSH secretion at the pituitary level. As for prolactin, our results could indicate that TRH is a more potent stimulator of prolactin secretion than of TSH secretion, or that TSH and prolactin pituitary thresholds for TRH are different.     

Effects of pretreatment with adrenocorticotropin on endocrine and behavioral responses of bulls to sexual activity

Peripheral concentrations of cortisol, growth hormone and testosterone were determined in two experiments which examined the endocrine and behavioral responses of sexually mature Angus bulls to an estrous female (Experiment 1) and to female exposure 5 hours following an adrenocorticotropin (ACTH) injection (Experiment 2). Sexual activity of bulls in Experiment 1 significantly increased levels of cortisol when compared with concentrations before exposure to a female. Administration of ACTH in Experiment 2 consistently elevated levels of cortisol by 30-fold (P<0.01) when compared with pre-ACTH concentrations. This heightened level of cortisol persisted throughout the period of exposure to an estrous cow, although a gradual decline in cortisol concentrations occurred over time (P<0.05). In Experiment 1, growth hormone profiles tended to increase in response to sexual activity (P<0.10), whereas in Experiment 2, growth hormone increased in response to ACTH administration (P<0.01) and to female exposure (P<0.01). Concentrations of testosterone were unaffected (P>0.10) by mating activity in Experiment 1. In Experiment 2, acute suppression (P<0.01) in testosterone concentrations 5 hours after ACTH administration coincided with the exposure period to the estrous female. Frequencies of mounting behavious (penis extension, mounting, intromission and ejaculation) exhibited by ACTH-treated bulls were significantly lower compared with the frequencies two days earlier. Exogenous ACTH administration suppressed reproductive behaviors of bulls and altered secretion of cortisol, growth hormone and testosterone. Furthermore, these data provide evidence that specific mating behaviors of the bull can be influenced by circulating steroids.     

Serotoninergic drugs affect prolactin and growth hormone secretion in the domestic fowl

Adult fowl of both sexes injected with the monoamine oxidase inhibitor pargyline showed elevated circulating prolactin concentrations and reduced growth hormone concentrations. Young cockerels injected with the serotonin agonist quipazine and the antagonist methysergide showed responses consistent with a serotoninergic stimulatory control of prolactin. Injection of the serotonin precursor tryptophan and the serotonin re-uptake blocker imipramine resulted in elevated prolactin and reduced growth hormone levels. The similarities and differences in the control of prolactin and growth hormone in birds and mammals were discussed.     

Pituitary responsiveness to gonadotrophin-releasing and thyrotrophin-releasing hormones in children receiving phenobarbitone.

The effect of long-term treatment with phenobarbitone on pituitary responsiveness to gonadotrophin-releasing hormone and thyrotrophin-releasing hormone was studied in 20 boys being treated with the drug to prevent febrile convulsions. Baseline concentrations of luteinising and follicle-stimulating hormones were reduced as well as the responses of these hormones to stimulation with gonadotrophin-releasing hormone. Baseline prolactin concentrations were raised in comparison with those in normal children. The response of prolactin to thyrotrophin-releasing hormone, however, was impaired only in the children who had been receiving the drug for a long time. Phenobarbitone had no effect on the secretion of growth hormone. Further studies should be carried out to ascertain how long these effects on pituitary function last after phenobarbitone is withdrawn and whether this interference with pituitary function modifies the child''s subsequent development.     

Effect of fenfluramine on growth hormone and prolactin secretion in obese subjects

Obese subjects show a subnormal growth hormone (GH) and prolactin (PRL) release in response to a variety of stimuli. Fenfluramine, an anorexiant drug used in obesity therapy, may have some effects on hypothalamic-pituitary function mediated by serotoninergic stimulation. The present investigation in obese subjects was carried out to study the effects of fenfluramine (60 mg orally) on GH and PRL secretion after intravenous arginine infusion. Ten volunteer obese females were studied and compared with 10 volunteer normal weight controls. In the obese group the GH response to arginine was significantly lower than in control group. Fenfluramine administration restored the subnormal GH response to arginine in obese subjects. The PRL response to arginine in obese women was subnormal. Fenfluramine administration restored the response of PRL to arginine infusion to normal. In conclusion, fenfluramine--under acute circumstances--enhances the hypothalamic-pituitary response to arginine in obese subjects. The decreased GH and PRL output in obese subjects is not due to an absolute hormonal deficiency and this effect of fenfluramine on GH secretion may--due to its lipolysis stimulation--be useful in obesity treatment.     

Selective increase in plasma luteinising hormone concentrations in drug free young men with mania.

The hypothalamic-pituitary-gonadal system was investigated in drug free young men with either mania or acute schizophrenia and in age matched controls by measuring, at frequent intervals during a 17 hour "neuroendocrine day," plasma concentrations of luteinising hormone (LH), follicle stimulating hormone, prolactin, testosterone, sex hormone binding globulin (SHBG), and cortisol. Plasma LH in mania was significantly increased compared with the control value at all time periods and increased in the morning and evening samples compared with values in the schizophrenic patients. Plasma prolactin and cortisol concentrations were significantly greater in mania and schizophrenia compared with control values at several times during the day, but there were no significant between group differences in plasma testosterone or SHBG. These results show that in young men with mania there is a major disturbance in the central mechanisms that control the release of LH, the control of prolactin and cortisol secretion is abnormal in mania and acute schizophrenia, and plasma LH concentrations may provide a useful hormonal diagnostic test for mania.     

Autocrine regulation of mammary cell differentiation

Summary Milk secretion and mammary function in dairy animals are regulated by local mechanisms sensitive to the frequency or efficiency of milking. Acute local control of milk secretion occurs through autocrine feedback inhibition by a milk protein. Sustained changes in milking frequency and milk secretion are associated with longer-term adaptations in the degree of differentiation and, ultimately, the number of mammary epithelial cells. Differentiation of cultured mammary cells is suppressed by a milk fraction containing the inhibitor, suggesting that intra-mammary regulation of differentiation in vivo is elicited by the same autocrine regulator subsequent to its acute effect on milk secretion. The autocrine factor may affect mammary cell differentiation by modulating the number of cell surface hormone receptors for prolactin, thereby changing their sensitivity to circulating hormones.Dedicated to Professor Stuart Patton on the occasion of his 70th birthday.     

Effect of prolactin infused into the third ventricle on LH secretion in follicular-phase and ovariectomized ewes

This study tested a hypothesis that an acute enhancement of prolactin concentration within the central nervous system (CNS) would affect the LH secretion in ewes, depending on the level of endogenous estrogens in the organism. A 3-h long intracerebroventricular (icv.) infusion of ovine prolactin was made in late follicular-phase ewes, experiment 1, and in ovariectomized (OVX) ewes (experiment 2). No significant differences were found in mean LH concentrations and LH peak number before, during and after prolactin administration (50 microg/100 microl/h) in intact cyclic ewes. No diurnal rhythm in LH was detected in prolactin-infused ewes. From the two doses of prolactin used in OVX ewes (25 and 50 microg/100 microl/h) only the lower dose suppressed significantly the mean plasma LH concentration after the infusion, compared to those noted before (P < 0.01) and during (P < 0.001) prolactin treatment. Prolactin had no effect on LH pulse frequency in OVX ewes, however, a tendency to decrease in LH peak number was observed after administration of a lower dose. Plasma prolactin levels decreased significantly (P < 0.01 and P < 0.001) after the icv. infusion in all groups, indicating a high degree of effectiveness for exogenous prolactin at the level of the CNS.     

The regulation of ovine placental lactogen the role of the fetal hypothalamic-pituitary axis

The possible r?le of the fetal hypothalamic-pituitary axis in regulating the secretion of ovine placental lactogen (oPL) was investigated in chronically-catheterised ewes and fetuses in late pregnancy. Intravascular administration of agents to fetuses that significantly increased fetal prolactin concentrations (chlorpromazine 6.25 mg;thyrotrophin releasing hormone, 10 micrograms), significantly reduced fetal prolactin concentrations (bromocriptine, 0.033 mg/h), or significantly reduced fetal growth hormone (GH) concentrations (somatostatin, 2.5 micrograms/min), had no effect on maternal or fetal oPL concentrations. Mean fetal levels of prolactin or GH in late gestation could not be correlated with oPL concentrations, although fetal hypophysectomy prevented the normal prepartum fall in oPL concentrations.     

Photoperiodic regulation of glutamatergic stimulation of secretion of luteinizing hormone in male Syrian hamsters.

It has been suggested that changes in endogenous glutamatergic stimulation of secretion of luteinizing hormone (LH) induced by photoperiod play a role in regulating seasonal cycles of reproductive activity. The aim of this study was to test the hypothesis that the glutamatergic control of the secretion of LH in the male Syrian hamster is sensitive to photoperiod, by determining whether the glutamate agonist N-methyl-D-aspartate (NMDA) could stimulate LH secretion in this species and, if so, to determine whether the response varied among animals exposed to different daylengths. In the first experiment, adult male hamsters were housed in either short day (8 h light: 16 h dark) for 6 weeks to induce testicular regression, or long days (16 h light: 8 h dark) to maintain testicular function, and the effects of systemic administration of NMDA on serum LH concentrations were determined. In the short-day hamsters, all s.c. doses of NMDA (25-75 mg kg-1 body weight) produced a robust rise in serum LH concentrations within 15 min. In the long-day hamsters, basal LH concentrations were higher than in short-day hamsters, but only the highest dose of NMDA produced a significant increase in LH concentrations, and the magnitude of this increment was less than those observed in short days. In hamsters in long days, the low doses of NMDA that did not significantly alter LH concentrations nevertheless significantly suppressed serum prolactin concentrations, demonstrating the efficacy of the drug. In hamsters in short days, serum prolactin concentrations were at the limit of detection of the assay, so no inhibitory effect of NMDA on prolactin secretion could be determined on this photoperiod. In the second experiment, the effects of a fixed dose of NMDA (50 mg kg-1 body weight) was tested at intervals in hamsters exposed to short days for a prolonged period such that their testes initially regressed, but then became scotorefractory and testicular recrudescence occurred. After 6 and 12 weeks in short days, NMDA stimulated LH secretion. However, after 24 weeks in short days when testicular recrudescence was complete, the response to NMDA was lost. A third experiment determined whether the reduced response to NMDA in hamsters on long days relative to those in short days might result from higher concentrations of circulating testosterone. Hamsters in long days were castrated to remove the influence of gonadal feedback, and the response to NMDA tested 3 weeks later when endogenous LH concentrations had risen to levels characteristic of the chronically castrated condition.(ABSTRACT TRUNCATED AT 400 WORDS)     

A neuroendocrine model for prolactin as the key mediator of seasonal breeding in birds under long- and short-day photoperiods

Seasonal breeding is associated with sequential increases in plasma luteinizing hormone (LH) and prolactin in the short-day breeding emu, and in long-day breeding birds that terminate breeding by the development of reproductive photorefractoriness. A model of the avian neuroendocrine photoperiodic reproductive response is proposed, incorporating a role for prolactin, to account for neuroendocrine mechanisms controlling both long- and short-day breeding. The breeding season terminates after circulating concentrations of prolactin increase above a critical threshold to depress gonadotropin releasing hormone (GnRH) neuronal and gonadotrope (LH) activity. Subsequently, photorefractoriness develops for prolactin secretion and for LH secretion, independently of high plasma prolactin. The breeding season in the emu is advanced compared with long-day breeders, because after photorefractiness for both LH and prolactin secretion is dissipated, plasma concentrations of both hormones increase to maximum values while days are still short.     

Effect of chronic caffeine administration on theophylline concentrations required to produce seizures in rats

Caffeine as well as the antiasthmatic drug theophylline can cause seizures when administered to humans or animals in excessive doses. Studies on rats have shown rapid development of functional tolerance to caffeine-induced seizures whereas repeated pretreatment with theophylline had no significant effect on the theophylline concentrations required to produce seizures. The purpose of this investigation was to determine whether chronic exposure to caffeine can affect susceptibility to the convulsant effect of theophylline. Rats received caffeine, 40 mg/kg, or solvent twice a day for 7 days as an intravenous injection. On the eighth day, theophylline was infused intravenously until the onset of maximal seizures. At this pharmacologic end point, rats pretreated with caffeine had significantly higher theophylline concentrations in the brain and cerebrospinal fluid than did control (solvent-pretreated) animals. Although the concentration differences were relatively small (approximately 11%), they demonstrate in principle the development of caffeine-induced tolerance to the neurotoxic effect of theophylline. Additional experiments showed that the caffeine effect on theophylline neurotoxicity is not acutely mediated by paraxanthine, a major metabolite of caffeine.     

Methylenedioxymethamphetamine (MDMA; Ecstasy) suppresses IL-1beta and TNF-alpha secretion following an in vivo lipopolysaccharide challenge

In this study we examined the effects of methylenedioxymethamphetamine (MDMA) administration on responsiveness to an in vivo immune challenge with lipopolysaccharide (LPS; 100 microg/kg; i.p.). LPS produced an increase in circulating IL-1beta and TNF-alpha in control animals. MDMA (20 mg/kg; i.p.) significantly impaired LPS-induced IL-1beta and TNF-alpha secretion. The suppressive effect of MDMA on IL-1beta secretion was transient and returned to control levels within 3 hours of administration. In contrast, the MDMA-induced suppression of TNF-alpha secretion was evident for up to 12 hours following administration. In a second study we examined the effect of co-administration of MDMA (5, 10 and 20 mg/kg; i.p.) on LPS-induced IL-1beta and TNF-alpha secretion, and demonstrated that all three doses potently suppressed LPS-induced TNF-alpha secretion, but only MDMA 10 and 20 mg/kg suppressed LPS-induced IL-1beta secretion. In addition, serum MDMA concentrations displayed a dose-dependent increase, with the concentrations achieved following administration of 5 and 10 mg/kg being in the range reported in human MDMA abusers. In order to examine the possibility that the suppressive effect of MDMA on IL-1beta and TNF-alpha could be due to a direct effect of the drug on immune cells, the effect of in vitro exposure to MDMA on IL-1beta and TNF-alpha production in LPS-stimulated diluted whole blood was evaluated. However IL-1beta or TNF-alpha production were not altered by in vitro exposure to MDMA. In conclusion, these data demonstrate that acute MDMA administration impairs IL-1beta and TNF-alpha secretion following an in vivo LPS challenge, and that TNF-alpha is more sensitive to the suppressive effects of MDMA than is IL-1beta. However the suppressive effect of MDMA on IL-1beta and TNF-alpha could not be attributed to a direct effect on immune cells. The relevance of these findings to MDMA-induced immunomodulation is discussed.     

Influence of short days on diurnal patterns of serum gonadotrophins and prolactin concentrations in the male Djungarian hamster, Phodopus sungorus

Exposure to short days for 8 weeks suppressed mean serum concentrations of FSH, LH and prolactin compared to hamsters kept in long days. Hamsters in short days exhibited a small afternoon rise in serum FSH, but serum LH and prolactin did not exhibit 24-h variations. In hamsters under long days, a late afternoon-early evening increase was evident for circulating prolactin but none was detected for the gonadotrophins. A fall in testes weights rapidly occurred by 14-28 days after transfer to short days. This was accompanied or preceded by a decrease in serum gonadotrophins and prolactin. Reductions in serum FSH and LH occurred in short days in blood samples taken at 09:00 h or 15:00 h. However, the nadir in serum prolactin was first achieved (at 09:00 h), at least 7 days before that at 15:00 h (i.e. Day 14 versus Day 21 of short photoperiod, respectively). The ability to secrete gonadotrophins was further tested in hamsters that had undergone gonadal regression. Castration of hamsters exposed to short days or injected with melatonin in the afternoon, a treatment known to mimic short day effects, induced a 3- to 5-fold increase in serum gonadotrophins. However, this rise in FSH and LH was significantly attenuated compared to the 10-fold response in controls in long days. The results indicate that gonadal involution induced by short days may be mediated by the decline in mean gonadotrophin secretion which, in turn, is regulated by responsiveness to steroids, as well as a mechanism independent of the negative feedback action of gonadal steroids.     

Exercise increases prolactin-receptor expression on human lymphocytes.

Plasma prolactin has been shown to increase during stress; the immune system is responsive to prolactin and affected by stress. Therefore, this study was undertaken to investigate the effects of acute graded, maximal treadmill exercise on prolactin-receptor expression by lymphocytes. Eight healthy men underwent one exercise and one nonexercise session. Blood was sampled immediately before and after the exercise. On the day of the nonexercise session, two resting blood samples were obtained at the same times as the exercise session samples to act as baseline data. Plasma prolactin concentrations were significantly elevated in response to exercise and correlated positively with total prolactin-receptor expression per B lymphocyte. An increase in total prolactin-receptor expression per B lymphocyte in response to exercise also was observed. In addition, exercise significantly increased the total number of circulating B lymphocytes expressing prolactin receptor as well as the total number of circulating B lymphocytes. These data support the idea that exercise may enhance the interaction between immune target cells and prolactin, a stress hormone capable of enhancing immune function.     

The effect of acute or chronic administration of prolactin on renal function in feral chickens

The role of the hormone prolactin in avian osmoregulation has not been clearly defined. The increases in plasma prolactin concentrations which have been demonstrated in previous studies in response to osmotic stress are strongly suggestive of a role for prolactin in avian osmoregulation. The present study investigated the effects of either acute or chronic administration of ovine prolactin on plasma electrolytes and renal function in the feral chicken. The effect of acute administration of prolactin depended on the dose of prolactin used. All plasma concentrations of prolactin achieved by the infusions were greater than reported values for endogenous prolactin. Acute infusion of prolactin at the lower dose increased the fractional excretion of sodium and chloride significantly, whereas the higher dose of prolactin had no effect. However, chronic administration of ovine prolactin had no significant effects on plasma electrolytes and renal function. It is possible that the role of prolactin in avian osmoregulation is a combination of its effects on the kidneys and also on extrarenal tissues such as the intestine and nasal salt glands (where present). Accepted: 22 August 1997     

Characterization of the inhibitory effects of hyperprolactinaemia on the mechanism controlling LH secretion in chronically ovariectomized rats

The time-course of the inhibitory effect of hyperprolactinaemia on LH secretion was delineated. Hyperprolactinaemia was induced in ovariectomized rats with injections of domperidone or ovine prolactin and circulating LH levels were measured from 1 h to 9 days after the treatment. Inhibition of LH secretion occurred within 2-4 h after treatment, and was maintained (provided that serum prolactin remained elevated) for a period of 6 days only. Thereafter LH levels increased to become insignificantly different from control levels on Day 9. A reduction in pituitary responsiveness was not associated with the acute or sub-chronic inhibition of LH secretion, although a significant fall in responsiveness was observed simultaneously with the return of serum LH levels to control values. No changes in hypothalamic LH-RH content was found. It is concluded that an impairment of pituitary function is not responsible for the inhibitory action of prolactin on LH secretion.