PROLACTIN STIMULATION TEST WITH PERPHENAZINE: AN EVALUATION OF PLASMA PROLACTIN LEVELS AND PITUITARY SECRETORY ACTIVITY IN THE RAT

1976 ◽  
Vol 68 (3) ◽  
pp. 355-368 ◽  
Author(s):  
A. A. VAN DER GUGTEN ◽  
P. C. SAHULEKA ◽  
G. H. VAN GALEN ◽  
H. G. KWA

SUMMARY Many investigations of the regulation of prolactin synthesis and release are based on single plasma prolactin determinations. The purpose of the present experiment was to ascertain whether groups of rats (i.e. young or adult, male or female animals, being either intact, gonadectomized or gonadectomized and treated with oestrone), differing in age and/or endocrine status, will react to a single dose of perphenazine by an acute release of pituitary prolactin in proportion to their initial plasma prolactin levels. No consistent relation existed between the classification of the twelve groups of rats into three categories of basal plasma prolactin levels (i.e. < 20, 25–50, > 125 ng/ml) and their response to perphenazine. Even though all groups showed a highly significant increase of plasma prolactin levels the magnitude of the maximum prolactin response at 30 min varied greatly within the groups of one category and thus was not related to the initial prolactin levels. The effect of 14 days of oestrone treatment in increasing plasma prolactin levels in gonadectomized animals was greatest in young and adult male rats, less in young females and not significant in adult females. The results obtained after perphenazine treatment in the latter group made it clear that the effect of oestrogen treatment on prolactin release can be completely blocked by increasing synthesis and/or release of the prolactin-release inhibiting factor (PIF). Since perphenazine induces decrease of pituitary prolactin and a concomitant increase of plasma prolactin levels through lowered PIF-action, the positive effect of oestrogens on prolactin release (as observed in gonadectomized male and young female rats) apparently is caused by a different mode of action. The implications of these findings for the regulation of prolactin release, as affected by the endocrine status of the rat, is discussed. Moreover, comparison of prolactin lost from the pituitary and gained in the circulation of the experimental animals, with amounts of prolactin that were observed to disappear from plasma during the experiment, provided suggestive evidence that the capacity to synthesize and/or eliminate prolactin, after a sudden provoked release of the hormone, differed among the groups. The rates of synthesis by the pituitary, of release from the pituitary into the circulation as well as of elimination of the hormone from the circulation (equally involved in determining actual plasma levels) are thought, therefore, to be far more important for the elucidation of prolactin regulation than single plasma prolactin determinations.

1985 ◽  
Vol 107 (3) ◽  
pp. 325-329 ◽  
Author(s):  
H. Cohen ◽  
I. Sabbagh ◽  
P. Guillaumot ◽  
J. Bertrand

ABSTRACT In this study, aimed at investigating whether dopaminergic regulation of prolactin could be implicated in the hypoprolactinaemia observed in the IPL nude rat, dopaminergic inhibition of prolactin was suppressed using a catecholamine synthesis inhibitor α-methyltyrosine (MT) and a dopaminergic antagonist sulpiride. Adult male rats (IPL nude and normal) were injected through implanted atrial cannulae with either MT (250 mg/kg) or physiological saline (control). Rats were decapitated 2 h after the injection. Plasma prolactin levels, compared with basal values, increased by 15·6 ± 1·9 (s.e.m.)- and 5·89 ± 0·6-fold in IPL nude and normal rats respectively. This difference was highly significant. The pituitary prolactin content was decreased in both groups. In a second experiment, adult male IPL nude or normal rats were injected with either sulpiride (1 mg/kg) or saline and decapitated 2, 4, 8, 12, 14 and 24 h later. Plasma prolactin levels, compared with basal values, were increased in rats injected with sulpiride by 9·2 ± 1·8 and 3·4 ± 0·7-fold in IPL nude and normal rats respectively. The pituitary prolactin content was reduced more in IPL nude than in normal sulpiride-injected rats. These data suggest that prolactin secretion, as well as synthesis, is under an increased dopaminergic inhibition in the male IPL nude rat. J. Endocr. (1985) 107, 325–329


1986 ◽  
Vol 108 (3) ◽  
pp. 399-403 ◽  
Author(s):  
R. L. Pérez ◽  
G. A. Machiavelli ◽  
M. I. Romano ◽  
J. A. Burdman

ABSTRACT Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat. J. Endocr. (1986) 108, 399–403


2018 ◽  
Vol 314 (1) ◽  
pp. R12-R21 ◽  
Author(s):  
Hershel Raff ◽  
Brian Hoeynck ◽  
Mack Jablonski ◽  
Cole Leonovicz ◽  
Jonathan M. Phillips ◽  
...  

Care of premature infants often requires parental and caregiver separation, particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented by external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults that were exposed to hypoxia and spontaneous hypothermia as neonates. Exposure of neonates to daily hypoxia without spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines and that our rat model of prematurity with hypoxia without hypothermia alters adult testosterone dynamics.


Endocrinology ◽  
2019 ◽  
Vol 160 (3) ◽  
pp. 522-533 ◽  
Author(s):  
Nayara S S Aquino ◽  
Ilona C Kokay ◽  
Carolina Thörn Perez ◽  
Sharon R Ladyman ◽  
Patricia C Henriques ◽  
...  

Abstract Kisspeptin has been shown to stimulate prolactin secretion. We investigated whether kisspeptin acts through the Kiss1 receptor (Kiss1r) to regulate dopamine and prolactin. Initially, we evaluated prolactin response in a Kiss1r-deficient mouse line, in which Kiss1r had been knocked into GnRH neurons (Kiss1r−/−R). Intracerebroventricular kisspeptin-10 (Kp-10) increased prolactin release in wild-type but not in Kiss1r−/−R female mice. In ovariectomized, estradiol-treated rats, the Kiss1r antagonist kisspeptin-234 abolished the Kp-10–induced increase in prolactin release but failed to prevent the concomitant reduction in the activity of tuberoinfundibular dopaminergic (TIDA) neurons, as determined by the 3,4-dihydroxyphenylacetic acid/dopamine ratio in the median eminence. Using whole-cell patch clamp recordings in juvenile male rats, we found no direct effect of Kp-10 on the electrical activity of TIDA neurons. In addition, dual-label in situ hybridization in the hypothalamus of female rats showed that Kiss1r is expressed in the periventricular nucleus of the hypothalamus (Pe) and arcuate nucleus of the hypothalamus (ARC) but not in tyrosine hydroxylase (Th)–expressing neurons. Kisspeptin also has affinity for the neuropeptide FF receptor 1 (Npffr1), which was expressed in the majority of Pe dopaminergic neurons but only in a low proportion of TIDA neurons in the ARC. Our findings demonstrate that Kiss1r is necessary to the effect of kisspeptin on prolactin secretion, although TIDA neurons lack Kiss1r and are electrically unresponsive to kisspeptin. Thus, kisspeptin is likely to stimulate prolactin secretion via Kiss1r in nondopaminergic neurons, whereas the colocalization of Npffr1 and Th suggests that Pe dopaminergic neurons may play a role in the kisspeptin-induced inhibition of dopamine release.


2002 ◽  
Vol 368 (3) ◽  
pp. 783-788 ◽  
Author(s):  
Noriaki SHIBATA ◽  
Junya MATSUMOTO ◽  
Ken NAKADA ◽  
Akira YUASA ◽  
Hiroshi YOKOTA

Various adverse effects of endocrine disruptors on the reproductive organs of male animals have been reported. We found that UDP-glucuronosyltransferase (UGT) activities towards bisphenol A, testosterone and oestradiol were significantly decreased in liver microsomes prepared from adult male Wistar rats administered with the endocrine disruptor bisphenol A (1mg/2 days for 2 or 4 weeks). However, suppression of the transferase activities was not observed in female rats, even after bisphenol A treatment for 4 weeks. Diethylstilbestrol, which is well known as an endocrine disruptor, had the same effects, but p-cumylphenol had no effect on UGT activities towards sex hormones. Co-administration of an anti-oestrogen, tamoxifen, inhibited the suppression of the transferase activities by bisphenol A. Western blotting analysis showed that the amount of UGT2B1, an isoform of UGT which glucuronidates bisphenol A, was decreased in the rat liver microsomes by the treatment. Northern blotting analysis also indicated that UGT2B1 mRNA in the liver was decreased by bisphenol A treatment. The suppression of UGT activities, UGT2B1 protein and UGT2B1 mRNA expression did not occur in female rats. The results indicate that bisphenol A treatment reduces the mRNA expression of UGT2B1 and other UGT isoforms that mediate the glucuronidation of sex hormones in adult male rats, and this suggests that the endocrine balance may be disrupted by suppression of glucuronidation.


1992 ◽  
Vol 29 (4) ◽  
pp. 288-300 ◽  
Author(s):  
J. H. J. van Nesselrooij ◽  
C. F. Kuper ◽  
M. C. Bosland

The predictive value of elevated plasma prolactin concentrations for the presence of spontaneous pituitary lesions was studied in 40 male and 38 female Wistar (Cpb:WU) rats, all 30 months old. The pituitaries were examined light microscopically and stained for prolactin using immunohistochemical methods. Plasma prolactin concentrations were measured by radioimmunoassay. Pituitary lesions were classified on the basis of their morphology in hematoxylin and eosin-stained sections as foci of hypertrophic or hyperplastic cells and hemorrhagic, pleomorphic, or spongiocytic adenomas; no carcinomas were found. There were significantly ( P = 0.001) more female than male rats with pituitary adenomas (58% females, 33% males) or without any pituitary lesions (21% females, 5% males); however, there were less female (21%) than male rats (63%) with foci of hyperplastic and/or hypertrophic cells but no adenomas in the pituitary ( P = 0.001). Elevation of plasma prolactin concentration above the upper 99th percentile value in age-matched rats without lesions was predictive, but not conclusively, of the presence of pituitary hemorrhagic adenomas in both sexes. It was, however, not predictive of the presence of foci of hypertrophic or hyperplastic cells. Elevation of plasma prolactin concentration above 10 ng/ml in male and 60 ng/ml in female rats was conclusive for the presence of hemorrhagic adenomas. Using multivariate analysis, significant positive correlations ( P < 0.01) were found between plasma prolactin concentration and presence and size of hemorrhagic adenomas and their prolactin staining intensity (correlation coefficients between 0.392 and 0.652). Foci of hyperplastic cells stained positively for prolactin, whereas hypertrophic cell foci and pleomorphic and spongiocytic adenomas did not stain for prolactin. There were no correlations (coefficients of less than ± 0.189) between plasma prolactin concentration and the presence of hypertrophic or hyperplastic cell foci and pleomorphic or spongiocytic adenomas in the pituitary. The morphologic criteria developed to distinguish spontaneous hypertrophic, hyperplastic, and neoplastic lesions of the rat pituitary corresponded well with their prolactin immunoreactivity and/or ability to elevate plasma prolactin concentration. These criteria constitute a biologically meaningful classification system for these rat pituitary lesions.


1972 ◽  
Vol 54 (2) ◽  
pp. 263-NP ◽  
Author(s):  
R. RELKIN ◽  
M. ADACHI ◽  
S. A. KAHAN

SUMMARY The effects of constant light, constant darkness and diurnal lighting, in combination with pinealectomy or sham-pinealectomy, on pituitary and plasma concentrations of radioimmunoassayable prolactin were investigated in 8-week-old male and virgin female rats. Two to three days after operation random groups of pinealectomized and sham-pinealectomized animals of the same sex were placed together in either continous light, continuous darkness or diurnal light, and killed 21 days later. Compared with sham-operated diurnally-illuminated controls, constant darkness caused a decrease in pituitary prolactin content and a rise in plasma prolactin levels. Pinealectomy or constant illumination reversed the effect of constant darkness, resulting in an increase in pituitary prolactin content and a fall in plasma prolactin levels when compared with sham-operated diurnally-illuminated controls. Electron microscopy of lactotrophic cells of the sham-pinealectomized animals exposed to constant darkness revealed few cytoplasmic granules, whereas these cells in the sham-pinealectomized animals exposed to constant light contained abundant granules; compared with the former groups, lactotrophic cells of sham-pinealectomized rats exposed to diurnal lighting revealed an intermediate degree of granulation.


1983 ◽  
Vol 61 (7) ◽  
pp. 676-684 ◽  
Author(s):  
R. Collu ◽  
J. R. Ducharme ◽  
D. Eljarmak ◽  
A. M. Marchisio ◽  
J. Bertrand ◽  
...  

Whilc a first injection of the antidopaminergic benzamide drug, sulpiride, induced a large rise in plasma prolactin (PRL) levels in chronically cannulated adult male rats, a second injection given 2 h later was totally inactive although the pituitary content of the hormone was still 76% of the initial value. When the second injection was given 8 h after the first it was slightly effective, but when administered 24 h later it was as effective as the first. The second of two consecutive injections of haloperidol given at 2-h intervals, or an injection of morphine given 2 h after sulpiride, were incapable of inducing a release of PRL. Two hours after an injection of sulpiride, a 30-min period of immobilization stress induced a significant rise in plasma PRL levels. A significant rise in plasma PRL levels was also observed when larger doses of sulpiride were given 2 h after a first injection of the drug. Apomorphine was at least as effective an inhibitor of PRL secretion when given 2 h after sulpiride than when injected after saline. In vitro studies of dopaminergic binding sites revealed the presence, in pituitary glands of sulpiride-treated rats, of receptors not modified by the drug. These data suggest that the only plausible explanation for the ineffectiveness of the second of two consecutive injections of sulpiride is the development of a state of refractoriness of the mechanisms that subserve the release of PRL induced by suppression of the inhibitory dopaminergic tonus.


1977 ◽  
Vol 73 (1) ◽  
pp. 67-70 ◽  
Author(s):  
SAM SHUSTER ◽  
WENDY M. HINKS ◽  
A. J. THODY

SUMMARY The effect of progesterone on the rate of sebum secretion was examined in intact and gonadectomized rats. In intact, adult, male rats, progesterone administered for 3 weeks decreased sebum secretion; after castration of adult males, progesterone increased sebum secretion and an even greater response occurred in males castrated at 21 days of age. In intact, adult, female rats progesterone slightly increased sebum production. As in the male, the response was affected by the time of gonadectomy, a greater response occurring after spaying at 21 days compared with 10 weeks of age. Thus, the response to progesterone in the adult rat differs in intact males and females and is affected by changes in the endocrine environment induced by gonadectomy, especially near the time of puberty.


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