Pituitary-grafted Animals Research Articles

Possible interactions of cyclosporine and hyperprolactinemia modulating the episodic secretion of prolactin.

The interrelationship between the effects of prolactin and cyclosporine (CsA) appears to be very complex and until now poorly understood. The aim of the present work was to analyze whether chronic treatment with CsA could modify the episodic secretion of prolactin in male rats and whether the presence of an ectopic pituitary could counteract the effects of the drug on the pulsatile secretion pattern of this hormone. At 30 days of age, male rats were implanted with one anterior pituitary under the kidney capsule or where sham-operated. Both pituitary-grafted and sham-operated rats were injected sc for 30 days with the vehicle or CsA (5 mg/kg/day), beginning on the day of surgery. Pituitary grafting and/or CsA administration changed the pulsatile secretion pattern of prolactin. In pituitary-grafted male rats, mean serum prolactin levels, absolute pulse amplitude, and half-life of the hormone increased, while the pulse frequency decreased, compared with the values found in sham-operated rats. CsA administration to sham-operated rats increased the relative amplitude of prolactin peaks and diminished the half-life of the hormone, compared with rats of the same group treated with vehicle. However, CsA treatment in pituitary grafted rats led to lower mean serum prolactin levels and absolute amplitude, while the frequency, duration, and relative amplitude of prolactin pulses were not modified. Plasma prolactin levels did not change in control animals, whereas a reduction in circulating values of the hormone was found in pituitary grafted animals. These data suggest that CsA modifies the pulsatile secretory pattern of prolactin in pituitary-grafted male rats. The different effects observed in the control and pituitary-grafted animals might be due to a direct effect of the drug on the ectopic lactotrophs that are submitted to local regulatory influences different from those of the in situ pituitary which are submitted to the regulatory influence of the hypothalamus.

Effects of luteinizing hormone-releasing hormone on pulsatile prolactin secretion in adult hyperprolactinemic female rats.

Regulation of prolactin secretion involves complex interactions of multiple inhibitory and stimulatory factors. Among them, luteinizing hormone-releasing hormone (LHRH) has been shown, when analyzed in single samples, to exert both stimulatory and inhibitory influences on prolactin secretion. In the present study, we have further examined the effects of LHRH on prolactin secretion by studying the pulsatile pattern of the hormone after the administration of the neuropeptide. For this purpose, adult sham-operated and pituitary-grafted female rats, exhibiting diestrus smears were bled for 3 hr during the morning (1030 to 1330 hr). Two pulses of LHRH (10 ng/kg body wt) were administered 60 and 120 min after starting the bleeding period. Pituitary grafting increased the mean serum prolactin levels, absolute amplitude of the hormone peaks, and its mean half-life, compared with control animals. In sham-operated rats, LHRH administration diminished mean serum prolactin levels, the absolute pulse amplitude and frequency of prolactin peaks. In pituitary-grafted animals, LHRH administration only decreased the pulse frequency of prolactin peaks. These data suggest that LHRH significantly suppressed pulsatile prolactin secretion, and that this effect was blunted by exposure to previously elevated circulating prolactin levels.

Changes in mediobasal hypothalamic dopamine and indoleamine metabolism after superior cervical ganglionectomy of rats.

Eight days after bilateral superior cervical ganglionectomy (Gx) of rats, norepinephrine content of medial basal hypothalamus (MBH) decreased significantly by 44-50%. To obtain information on other possible neurochemical sequela of Gx in MBH, we examined the metabolism of dopamine and serotonin in MBH of Gx rats by employing a high pressure liquid chromatography procedure. Eight days after Gx, MBH dopamine levels augmented significantly. Assessment of dopamine metabolism by measuring dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid (HVA)/dopamine indexes indicated a significant decrease of MBH DOPAC/dopamine ratio after Gx. MBH serotonin levels increased, and 5-hydroxyindoleacetic acid (5-HIAA)/serotonin index decreased significantly in Gx rats. To examine the interaction Gx-induced changes on MBH dopamine and serotonin with the modified hormonal milieu produced by an ectopic pituitary transplant, adult male rats bearing an ectopic pituitary within the pectoral muscles from day 5 of life were submitted to Gx on day 60 of life and were studied 8 days later. MBH dopamine content increased significantly after pituitary grafting, an effect counteracted by a subsequent Gx, while Gx alone augmented MBH dopamine levels. DOPAC and HVA contents augmented in pituitary-grafted animals, an effect counteracted by Gx. Gx increased MBH serotonin content in control but not in pituitary-grafted rats. After pituitary grafting a decrease in MBH 5-HIAA levels was found, an effect reversed by Gx. Pituitary transplants brought about a significant increase of MBH DOPAC/dopamine index, and a significant decrease in 5-HIAA/serotonin index, both effects being counteracted by Gx. Gx of control rats resulted in a significant decrease of MBH 5-HIAA/serotonin index. Analyzed as a main effect in a factorial analysis of variance, Gx decreased MBH DOPAC/dopamine and HVA/dopamine indexes significantly. Plasma prolactin increased in pituitary-grafted rats, an effect further increased by a subsequent Gx. In pituitary-grafted, Gx rats plasma GH levels augmented significantly. The data suggest that superior cervical ganglion removal affects differentially dopamine and indoleamine metabolism in MBH of control and pituitary-grafted rats.

Cyclosporine Effects on in vitro Responsiveness of Anterior Pituitary Hormone Release to Dopamine and Thyrotropin‐Releasing Hormone in Young Female Rats

Endocrine side effects of the immunosuppressive drug cyclosporine (CyA) include changes in anterior pituitary hormone secretion. The aim of the present study was to examine the effects of CyA on the responsiveness of in situ and ectopic anterior pituitary prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) release response to dopamine (DA) and thyrotropin-releasing hormone (TRH) treatment in young female rats, and to evaluate the possible PRL participation in these effects. Thirty day old rats were rendered hyperprolactinemic by transplanting an anterior pituitary gland of a littermate donor, under the kidney capsule, and were then injected with CyA or vehicle for 2 or 8 days. Sham-operated rats were used as controls and treated in the same way. CyA treatment prevented the increase in plasma PRL levels which occurred in controls after pituitary grafting. In vitro basal PRL release of in situ pituitaries from either sham-operated and/or pituitary-grafted animals was decreased by CyA treatment at any point studied. Basal in vitro secretion of GH was only decreased in the in situ pituitaries from grafted animals after 2 days of CyA therapy. The presence of an ectopic pituitary lead to an increase in the in vitro basal LH secretion from in situ pituitaries as compared to those from sham-operated rats. Basal LH release rates were not changed by CyA treatment, although the LH release in vitro did increase in the in situ pituitaries from sham-operated animals treated with the drug for 2 days. DA addition to the incubation media decreased the in vitro release of PRL, GH and LH from the in situ pituitaries of sham-operated and pituitary-grafted animals treated with vehicle. In CyA treated animals, DA decreased in vitro PRL release from the in situ pituitaries of animals, independently of the presence or absence of an ectopic pituitary. Reductions of the in vitro GH and LH release release after DA treatment were higher in the in situ pituitaries from grafted animals on day 8 of CyA or vehicle treatment. TRH increased the in vitro release of the three hormones with differential effects related to the length of the treatment with CyA and/or the presence of an ectopic pituitary. In vitro release of PRL and GH by ectopic pituitaries was inhibited by previous treatment with CyA and this effect was decreased proportional to the duration of the treatment with the drug, while LH secretion was not modified. Addition of DA to the incubation media resulted in a marked reduction of in vitro PRL and GH release, but only at day 8 of vehicle treatment on GH release did DA addition to media further decrease the release of both hormones from ectopic pituitaries from animals treated for 2 or 8 days with the drug, whereas LH secretion was not modified. TRH addition to the incubation media of ectopic pituitaries surprisingly reduced PRL and GH secretion on day 8 of CyA treatment or after surgery. The results of these studies suggest that CyA can act directly at the hypophyseal level modifying pituitary responsiveness to external stimuli. CyA seems to exert its main effects on lactotroph activity while its effects on somatotrophs and gonadotrophs are less.

Possible changes in the regulatory mechanisms of pulsatile luteinizing hormone secretion in adult pituitary-grafted female rats.

It is well known that LH is released in an episodic fashion. However, the effects of hyperprolactinemia on luteinizing hormone (LH) pulsatility are not fully understood. The present study was undertaken to describe hyperprolactinemia effects on the regulatory mechanism of LH pulsatility. For this purpose hyperprolactinemia was induced in female rats by the transplantation of two pituitary glands beneath the kidney capsule. Age-matched sham-operated animals were used as controls. We have evaluated the pulsatile pattern of LH in both groups of animals. As expected, pituitary grafting increased mean serum prolactin levels compared with the values found in control animals. Luteinizing hormone-releasing hormone (LHRH) administration did not change serum prolactin levels in control or in pituitary-grafted rats. Thyrotropin-releasing hormone (TRH) administration increased prolactin secretion in both groups. There is an increase in mean values of LH and in the absolute amplitude of LH peaks in pituitary-grafted compared with control rats. No other parameters of LH pulsatility were changed by pituitary grafting. After LHRH administration, LH release was increased and a priming effect after the second administration of LHRH is observed in control rats. In pituitary-grafted animals the responses of LH to LHRH administration was diminished compared with the response observed in control rats. The administration of two pulses of TRH to control rats only decreases the duration of LH pulses. However, in pituitary-grafted animals, TRH administration was followed by a decrease in the mean values of LH and in the absolute amplitude of the LH peaks. Vasoactive intestinal peptide (VIP) administration increased mean values of LH and the absolute and relative amplitudes of LH pulses in sham-operated animals, whereas only the relative amplitude of LH peaks was modified by VIP in pituitary-grafted rats. All these data suggest that hyperprolactinemia induced by pituitary-grafting interfere with the neuromodulator effects on the pulsatile regulatory center of the hypothalamus.

Effects of cyclosporine on ovarian function in sham-operated and pituitary-grafted young female rats.

Effects of cyclosporine (CyA) on ovarian function and the possible role of prolactin in mediating these effects were examined in young female rats. The animals were sham-operated or rendered hyperprolactinemic by transplanting pituitary glands under the renal capsule. Cyclosporine prevented the increase in plasma prolactin levels in grafted rats. However, in sham-operated animals plasma prolactin levels were increased after 8 days of CyA treatment. Plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were reduced 8 days after pituitary grafting and increased by CyA at both Day 2 and Day 8 of treatment. The content of LHRH in the hypothalamus was not affected on Day 2 but was reduced on Day 8 after grafting on CyA therapy. Plasma estradiol levels were increased by CyA in sham-operated rats on Day 2 and 8 of treatment, and in pituitary-grafted rats on Day 8 of therapy. In sham-operated rats, ovarian estradiol content was reduced after 2 and after 8 days of CyA administration. In pituitary-grafted rats, the ovarian estradiol content was suppressed after 8 days, and CyA treatment prevented this effect. Ovarian estradiol release in vitro under basal conditions was greater in ovaries derived from 38-day-old than in those from 32-day-old animals. The ovarian estradiol response to human chorionic gonadotropin (hCG) in vitro was increased 2 days after pituitary transplantation. Administration of CyA for 8 days increased basal and hCG-stimulated estradiol release in both sham-operated and pituitary-grafted animals. The present findings suggest that CyA can alter ovarian function by acting directly at the gonadal level. However, a hypothalamic-hypophyseal site of action cannot be ruled out.

Physiological roles of thyrotrophin-releasing hormone and vasoactive intestinal peptide on the pulsatile secretory patterns of prolactin in pituitary-grafted female rats.

Much is known about the fact that thyrotrophin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulate prolactin secretion but areas of uncertainty remain. This work was undertaken to describe the effects of TRH and VIP on the pulsatile secretion pattern of prolactin, in adult sham-operated and pituitary-grafted hyperprolactinaemic female rats. Two pulses of TRH (1 microgram/rat) or one pulse of VIP (20 micrograms/rat) were given 60 or 120 min after the period of blood sampling. Pituitary grafting increased the mean values of prolactin, absolute amplitude and duration of the peaks and decreased their frequency, compared with control animals. In sham-operated rats, TRH elevated prolactin levels by increasing the absolute and relative amplitudes and duration of the pulses, along with a decrease in their frequency. No priming effects of TRH were observed in this study. Hyperprolactinaemia blunted TRH effects on the pulsatile secretion pattern of prolactin. In sham-operated rats, VIP administration increased the absolute and relative amplitudes of the prolactin peaks. None of the other parameters studied were changed. In pituitary-grafted animals, VIP administration increased the absolute and relative amplitudes of the prolactin peaks but to a lesser extent compared with controls. These data suggest that TRH and VIP affect prolactin pulsatility differentially. The effects of TRH and VIP were blunted to some extent by exposure to previously elevated circulating prolactin levels.

Induction of Specific Gelatinolytic Proteinases in the Lateral Prostate of Rats by Ectopic Pituitary Grafts1

Activities of plasminogen activator (PA) and gelatinolytic proteinase in the ventral, lateral, and dorsal lobes of the prostate were examined in rats with hyperprolactinemia, which was induced by implantation of ectopic pituitary grafts under the renal capsule. Weight and total DNA content of the lateral lobe increased significantly in rats receiving two pituitary glands as compared with values for the initial untreated group and the muscle-implanted control animals. No change in specific activity of PA was observed in any prostatic lobe for animals of different treatment groups. However, there was a lateral lobe-specific induction of gelatinolytic proteinase activity in pituitary-grafted rats. Two Ca(2+)-independent proteinase activities of approximately 26-28 and 88 kDa, and three calcium-sensitive proteinase activities of 59, 64, and 76 kDa were found in zymograms of lateral prostate extracts of the untreated initial group and the muscle-grafted control. The lateral prostate proteinase pattern of pituitary-grafted animals demonstrated intense activities of approximately 51, 53, 64, 76, and 135 kDa as well as weaker activities of 40, 43, 59, 85, 93, 105, and 125 kDa. Many of these proteinase activities were present in the secretion of the lateral prostate of the untreated initial controls, suggesting that hyperprolactinemia promotes secretion in the lateral prostate. Those proteinase activities that were not in the secretion were probably of intracellular origin and may play a role in cellular remodeling. Castration resulted in a decrease in activities of these proteinases, and this decrease was observed whether the pituitary grafts were retained or removed.

A local direct effect of pituitary graft on growth of the lateral prostate in rats

Prolactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague-Dawley rats in whom a 0.5 cm or 1.0 cm testosterone-filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty-one days later, serum prolactin levels were not elevated in pituitary-grafted animals and were not significantly different from those in muscle-grafted rats. The mean lateral prostate weight on the grafted side in pituitary-implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle-implanted rats. In pituitary-implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle-implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats.

Growth Hormone (GH) Secretion in the Pituitary-Grafted Male Rat:In VivoEffects of GH-Releasing Hormone and Isoproterenol andin VitroRelease by Individual Somatotropes*

Although the pituitary-grafted rat is a classic model of chronic PRL excess, the presence of somatotropes in grafted pituitary tissue indicates a potential for GH secretion. The current study was designed to investigate GH-releasing hormone (GRH)-induced GH secretion and beta-adrenergic inhibition of GH release in animals bearing ectopic pituitary tissue free from hypothalamic control. Positive findings with regard to these in vivo experiments led us to an initial determination of GH secretion by individual somatotropes from transplanted pituitary tissue. In litters of 10 30-day-old Fisher rats, 2 male animals received subcapsular renal grafts of 3 littermate pituitary glands each. Thirty-five days after grafting, 1 group received saline (SAL) followed by GRH, and the other received the beta-adrenergic agonist isoproterenol (ISO) followed by GRH. Blood samples were taken before and after SAL or ISO treatment, GRH was then infused, and sampling was continued. Plasma was assayed for GH and PRL, and the reverse hemolytic plaque assay was used to determine GH release by individual somatotropes from transplanted pituitary tissue. Plasma PRL was clearly elevated in pituitary-grafted compared to muscle-grafted animals, but there was no difference in either body weight gain or basal GH levels between the groups. As shown previously, ISO itself induced a brief release of GH due to its direct effect on the pituitary gland. The GH response to GRH was greater in pituitary-grafted animals than in muscle-grafted controls after both SAL and ISO. GRH-induced GH release was suppressed by ISO pretreatment in muscle-grafted animals, but not in pituitary-grafted animals. The reverse hemolytic plaque assay unequivocally showed that transplanted pituitary tissue was capable of tonic as well as GRH-stimulated GH release. These results demonstrate that despite similar basal GH levels, animals bearing pituitary grafts release significantly greater amounts of GH in response to GRH. The evidence for GH secretion by individual somatotropes from transplanted pituitary tissue directly shows the grafted tissue to be a source of GRH-stimulated GH. The lack of beta-adrenergic inhibition of GRH-induced GH release in pituitary-grafted animals is consistent with the hypothesis that beta-adrenergic inhibition of GRH-induced GH secretion is mediated by an effect on the hypothalamus.

Melatonin effects on prolactin secretion in pituitary-grafted female rats.

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration of PRL secretion in pituitary-grafted female rats. Melatonin administration resulted in a marked and rapid decrease of previously high plasma PRL levels in pituitary-grafted rats. Luteinizing hormone releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in both sham-operated and grafted animals given saline whereas a statistically significant increase was observed in grafted, melatonin-treated rats. Estradiol benzoate administration caused an increase in plasma PRL levels of greater magnitude in the afternoon than in the morning in sham-operated animals given saline whereas in grafted animals no response to estradiol benzoate was detected. Melatonin increased the plasma PRL response to estradiol benzoate in sham-operated rats as compared to vehicle-treated animals. A normalization of PRL response to estradiol benzoate was shown in melatonin-treated, pituitary grafted rats. While the suppressive effects of melatonin in plasma PRL levels of pituitary-grafted animals is substantial the mechanism of this inhibition remains unknown.

Melatonin effects on prolactin secretion in pituitary-grafted male rats.

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration on PRL secretion in pituitary-grafted male rats. Melatonin administration 5 hours before dark resulted in a marked decrease of previously high basal plasma PRL levels in pituitary-grafted rats, whereas a marked increase was detected in sham-operated animals. Vehicle treatment did not modify basal PRL values in grafted or sham-operated animals. Luteinizing hormone-releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in vehicle-treated, sham-operated or grafted rats, as well as in melatonin-treated sham-operated rats. An increase in PRL levels was shown in grafted rats treated with melatonin. Estradiol benzoate (EB) administration resulted in an increase in plasma PRL levels both in sham-operated and grafted vehicle-treated rats. No PRL response could be detected in sham-operated, melatonin-treated animals after EB administration. In pituitary-grafted animals given melatonin, PRL response to EB administration was slight and delayed. From these data, melatonin appears to modify PRL secretion through multiple complex mechanisms that may depend on the physiological status (hormonal and neurotransmitter) of the animals. A direct effect at the pituitary level altering lactotroph sensitivity seems to be one plausible explanation for the current findings, although an hypothalamic site of action cannot be excluded.

Catecholaminergic control of plasma growth hormone and thyrotropin levels in hypophysectomized rats bearing ectopic pituitary transplants

Transplantation of the anterior pituitary to an ectopic site leads to stimulation of PRL secretion and suppression of the release of other adenohypophyseal hormones. We have previously reported that precursors and blockers of catecholamine synthesis can affect PRL release from the ectopic pituitary. In the present study we have measured the effects of L-3,4-dihydroxyphenylalanine (DOPA), DL-threo-dihydroxyphenylserine (DOPS), α-methyl-paratyrosine (α-mpt) and diethyldithiocarbamate (ddc) on plasma growth hormone (GH) and thyrotropin (TSH) levels in hypophysectomized rats with pituitary transplants under the renal capsule. In these animals, peripheral plasma GH levels were elevated by a precursor (DOPA) and reduced by a blocker (α-mpt) of catecholamine synthesis. Plasma TSH levels were increased by a precursor (DOPS) and reduced by a blocker (ddc) of norepinephrine synthesis. We suspect that GH and TSH present in the circulation of pituitary-grafted animals were derived, in part, from the ectopic pituitary tissue and suggest that the small but detectable secretion of hormones other than PRL in this animal model is under the control of endogenous catecholamines.

Effects of chronic hyperprolactinemia on sexual arousal and erectile function in male rats.

Studies were conducted to determine if the inhibitory effects of chronic hyperprolactinemia on sexual behavior in male rats occur through reduced sexual arousal as opposed to reduced erectile function. Pituitary-grafted (hyperprolactinemic) and sham-operated, gonadally intact male rats were given standard tests of copulatory behavior, mounting behavior tests after genital anesthetization and penile reflex tests while restrained in a supine position. Beginning 7 days after pituitary transplantation, the number of erections displayed in penile reflex tests was significantly reduced in the pituitary-grafted animals. Increased intromission latencies and reduced intromission rates in tests of copulatory behavior were also observed at this time. Beginning 3-4 weeks after surgery, mounting rates were inhibited in hyperprolactinemic animals in both the copulatory behavior tests and tests of mounting behavior after genital anesthetization. Prolactin levels were significantly elevated in the pituitary-grafted animals, but serum testosterone levels were unaffected. To determine if the effects of hyperprolactinemia on erectile function occurred through changes in supraspinal input to neurons in the spinal cord controlling erectile function, pituitary-grafted and sham-operated male rats were subjected to spinal transection (between vertebral levels T6 and T9). Beginning 7 days later, penile reflex performance was re-examined. Hyperprolactinemic animals displayed significantly fewer erections during the initial test, but not in tests performed 10 and 13 days after spinal transection. The pituitary-grafted animals also showed a significant reduction in latency to the first erection with each successive test, suggesting a delayed recovery from increased supraspinal inhibitory input.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered sensitivity to an opiate antagonist, naloxone, in hyperprolactinemic male rats.

An increase in endogenous opiatergic tone has been suggested as a mechanism for suppression of gonadotropin release in hyperprolactinemia (hyperPRL). In an attempt to evaluate this possibility in hyperprolactinemic males, we have examined the effects of a specific opiate antagonist, naloxone, on plasma LH levels in adult male rats rendered hyperprolactinemic by transplanting two pituitary glands underneath the kidney capsule. Naloxone was administered intravenously (i.v.) at different dose levels (0.2,2, or 20 mg/kg body weight) and blood samples were collected at intervals ranging from 15 to 60 min after naloxone administration. In all experiments, plasma LH levels in the sham-operated controls were significantly increased after naloxone administration, while those in the pituitary-grafted group remained unaltered. Injecting naloxone daily for 3 or for 10 days failed to alter plasma LH levels in both sham-operated and pituitary-grafted animals. Administration of LHRH induced a 7-fold increase in plasma LH levels in both the pituitary-grafted animals and the sham-operated controls. These studies demonstrate that hyperPRL interferes with the naloxone-induced rise in circulating LH levels in the male rat.

Does prolactin modify testosterone feedback in the hamster? Pituitary grafts alter the ability of testosterone to suppress luteinizing hormone and follicle-stimulating hormone release in castrated male hamsters.

Adult male golden hamsters maintained in a long photoperiod (14 h of light and 10 h of darkness) or in a short photoperiod (5 h of light and 19 h of darkness for 7 weeks) were castrated and either given one anterior pituitary transplant under the kidney capsule or sham-operated. Additional animals were castrated and grafted or sham-grafted at the time of transfer to the short photoperiod. Starting 2 weeks after castration, all animals were injected three times a week with 20 micrograms testosterone propionate (TP). After 3 weeks, the dose of TP was increased to 80 micrograms and, after an additional 2 weeks, to 320 micrograms per injection. Blood samples were collected 2 weeks after castration and 1 day after the last injection of 20, 80, and 320 micrograms TP. Short photoperiod reduced and pituitary grafts increased plasma PRL levels. Plasma testosterone levels were related to the dose of injected TP, but were not influenced by photoperiod or pituitary transplants. Before the onset of TP injections, plasma LH and FSH levels in grafted and sham-grafted hamsters did not differ. In each of the three photoperiod conditions, injections of TP were consistently less effective in suppressing plasma gonadotropin levels in pituitary-grafted animals than in sham-grafted controls. These results indicate that PRL modulates the effects of exogenous testosterone on LH and FSH release in adult castrated male golden hamsters, this effect of PRL is due to reducing the sensitivity of the hypothalamic-pituitary system to feedback inhibition by testosterone, and suppression of pituitary PRL release in short photoperiod may be partially responsible for the concomitant increase in the sensitivity of LH and FSH release to inhibition by testosterone.

Effects of hyperprolactinemia on copulatory behavior and testicular human chorionic gonadotropin binding in adrenalectomized rats.

Hyperprolactinemia (hyperPRL) induced by grafting four ectopic pituitary glands under the kidney capsules results in suppressed copulatory behavior, increased testicular hCG binding, and increased adrenal weights and plasma corticosterone levels. To determine whether stimulation of adrenal activity may be involved in the effects of hyperPRL on copulatory behavior and testicular hCG binding, we have examined the effects of four ectopic pituitary grafts in intact and adrenalectomized, corticosterone-replaced (1 mg, three times per week) male rats. Pituitary grafting resulted in significant elevations in plasma PRL levels and had a significant suppressive effect on male copulatory behavior in both intact and adrenalectomized animals. Plasma levels of FSH were suppressed in the adrenalectomized, pituitary-grafted animals but were significantly reduced only in the samples taken just before the rats were killed. In contrast, plasma LH was significantly lowered in both groups of grafted animals 6 weeks after the...

Effects of pituitary grafts on testosterone stimulated growth of rat prostate.

The effect of prolactin and testosterone on the lateral prosnatic growth was studied in Fischer 344 rats. Two pituitaries from adult female rats/animal were grafted under the renal capsule of 30day -old castrated males. The control castrates received surgical exposure of the kidney but no grafts. Silasnic tubing either empty or packed with crystalline testosterone for 0.5, 2.0 or 4.0 cm of its length was implanted s.c. into each ran immediately following the grafting or sham operation. Three weeks later, all animals were sacrificed. The average serum prolactin in pituitary-grafted ani mals was 430 ng/ml. In nongrafted controls, the average was 15—50ng/ml. In rats bearing pituitary grafts and 0.5 cm of testosterone tubing, lateral prostate weight was 88% greater than in controls given 0.5 cm of testosterone tubing alone. In animals with grafts and 2.0 cm testosterone tubing, the increase in lateral prostate weight was only 27%. Furthermore, in those given 4.0 cm testoster one tubing, lateral prostate weights in grafted and control animals were not significantly different. Pituitary grafts did not increase the weight of ventral prostate, dorsal prostate, seminal vesicle or coagulating gland beyond that stimulated by the testosterone tubing. Results demonstrated an in verse relationship between circulating testosterone levels and the degree of synergism with pro lactin on the weight of the lateral prostate in rats.