Cell proliferation in the rat pituitary gland: A mechanism of control in prolactin cells

Summary We investigated the relationship between prolactin content and DNA replication in the anterior pituitary gland. Thymidine incorporation in pregnant rats is significantly lower than in virgin controls. This is accompanied by a decreased activity of DNA polymerase. Sulpiride administration to pregnant rats enhances thymidine incorporation to levels similar to virgin controls. The results indicate a negative feedback between prolactin content and DNA synthesis in the rat anterior pituitary gland.We are grateful to Prof. Carlos J. Gómez for the opportunity to perform this work. These studies were supported by PLA-MIRH 99.178.1.78, by the Consejo Nacional de Investigaciones Científicas y Técnicas and by the Comisión Nacional de Energía Atómica (Argentina).     

DNA synthesis in the pituitary gland of the rat: effect of sulpiride and clomiphene.

Sulpiride administration to rats releases prolactin and increases DNA replication in the anterior pituitary gland. Clomiphene prevents the stimulation of DNA synthesis produced by sulpiride, but does not affect prolactin release from the gland. These findings suggest that the intracellular prolactin content of the anterior pituitary gland plays a role in the regulation of DNA synthesis through a mechanism mediated by oestrogens.     

DNA synthesis in the pituitary gland of the rat: Effect of sulpiride and clomiphene

Summary Sulpiride administration to rats releases prolactin and increases DNA replication in the anterior pituitary gland. Clomiphene prevents the stimulation of DNA synthesis produced by sulpiride, but does not affect prolactin release from the gland. These findings suggest that the intracellular prolactin content of the anterior pituitary gland plays a role in the regulation of DNA synthesis through a mechanism mediated by oestrogens.This work was supported by PLAMIRH 99.178.1.78, by the Consejo Nacional de Investigaciones Científicas y Técnicas and by the Comisión Nacional de Energía Atómica (Argentina). We are grateful to Dr P. Scacchi for performing the radioimmunoassay and to Prof. C. J. Gómez for the opportunity to perform this work.     

Effects of thyroidectomy and thyroxine replacement on the responsiveness of the anterior pituitaries from male rats to thyrotropin-releasing hormone in vitro

Summary Thyroidectomy decreased prolactin concentrations in the anterior pituitary (AP) and serum of the male rat. The amount of basal and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin by AP in vitro was lower in thyroidectomized (Tx) rats than in sham Tx rats. These results suggest that the inhibitory effects of thyroidectomy on pituitary and serum prolactin in male rats are mediated in part by the reduction of the production and spontaneous release of prolactin and the responsiveness of prolactin to TRH.     

Effects of constant light exposure and blindness on the oxidative metabolism of selected brain areas in male rats

Summary Male rats were housed in continous illumination or blinded when 21 day-old and killed 69 days later. The continuous illumination exposure increased the weights of testes and sex accessory organs and reduced the pineal gland weight. Blindness decreased weights of testes, sex accessory organs and anterior pituitary. The oxygen consumption rate of the hypothalamus was higher in the blinded animals than in the controls and lower in the continuously illuminated rats. No one of such groups showed significant changes in the oxygen consumption by either the amygdata or the hippocampus.     

The prolactin releasing peptides: RF-amide peptides

Although dopamine is considered the major hypothalamic controller of prolactin release from the anterior pituitary gland, there is evidence that a yet to be discovered prolactin releasing factor (PRF) also exists in brain. Recently, two peptides were isolated, products of the same prohormone, that were reported to have significant prolactin-releasing activity. These peptides, called prolactin releasing peptides, are not accepted by all investigators to be in fact PRFs. Instead, it appears that their widespread distribution in brain and the presence of receptors for the peptides in sites unrelated to neuroendocrine function are the basis for a variety of central nervous system action including activation of the autonomic nervous system. Thus, these peptides may not be PRFs, but instead neuroactive agents that are involved in many brain circuits with divergent functions.     

Inhibition by SMS 201-995 of normal mammary gland growth in mice

Twice daily s.c. injection of 5 ng or 50 ng of SMS 201-995 between 25 and 55 days of age induced a significant retardation of normal mammary gland growth in C3H/He virgin mice, associated with the reduced plasma GH level. Meanwhile, plasma prolactin level and the pattern of estrous cycle were affected little by SMS treatments. The results indicate an involvement of GH in normal mammary gland growth in mice.     

Inhibition by SMS 201-995 of normal mammary gland growth in mice

Summary Twice daily s.c. injection of 5 ng or 50 ng of SMS 201-995 between 25 and 55 days of age induced a significant retardation of normal mammary gland growth in C3H/He virgin mice, associated with the reduced plasma GH level. Meanwhile, plasma prolactin level and the pattern of estrous cycle were affected little by SMS treatments. The results indicate an involvement of GH in normal mammary gland growth in mice.     

Effects of prolactin and growth hormone on DNA synthesis of rat mammary carcinomas in vitro

Summary Explants derived from mammary carcinomas of DMBA-treated female Sprague-Dawley rats were cultured for 5 days in Medium 199 containing insulin and corticosterone. The addition of ovine prolactin to the culture media resulted in a consistent significant increase in H³-thymidine incorporation into DNA. DNA synthesis of explants treated with either ovine or human growth hormone was intermediary to prolactin-treated cultures and control cultures. A combination of prolactin and human growth hormone often increased DNA synthesis above either hormone alone, suggesting a possible growth synergism between these peptides.Supported by NIH research grant No. CA-13777 and American Cancer Society research grant No. ET-59.NIH Research Career Development Awardee No. CA-35027.     

Activity alterations of metabolic enzymes in the anterior pituitary of female rats during acute and chronic starvation,as well as after refeeding

Summary The activity of glycolysis and hexose monophosphate shunt decreases while the activity of some oxydative enzymes and acid phosphatase increases in the anterior pituitary of adult female rats during starvation. The alterations depend on the severity of starvation. The polypeptide hormone production also decreases. A close relationship exists between the metabolic activity of the gland and its endocrine function.     

Effects of Freund's complete adjuvant on the dirunal rhythms of neuroendocrine processes and ornithine decarboxylase activity in various tissues of male rats

The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.     

Pineal function cannot prevent the occurrence of castration cells in male rats

The relationship between the pineal gland and the pituitary gland was investigated in male rats. The results indicate that the hypothalamo-adenohypophysial-gonadal axis is affected by the pineal gland, but the appearance of castration cells following gonad ablation may be only slightly modified by alterations in pineal gland function.     

Pineal function cannot prevent the occurrence of castration cells in male rats

Summary The relationship between the pineal gland and the pituitary gland was investigated in male rats. The results indicate that the hypothalamo-adenohypophysial-gonadal axis is affected by the pineal gland, but the appearance of castration cells following gonal ablation may be only slightly modified by alterations in pineal gland function.     

Lesions in suprachiasmatic nuclei simulate effects of pinealectomy on prolactin release in ovariectomized and sulpiride-treated female rats

Summary Previous studies indicate that the pineal gland alters prolactin secretion, and it was suggested that at least part of the effect of the pineal hormone melatonin on prolactin release may be mediated by the hypothalamic structures. In this study, pinealectomy and lesions of the suprachiasmatic nuclei were found to alter serum levels of prolactin in the same direction, an effect that was counteracted by daily afternoon melatonin administration. Melatonin, but not other pineal indoles, also prevented sulpiride-induced prolactin secretion in pinealectomized or suprachiasmatic nuclei-lesioned and ovariectomized rats, which suggested that the pineal gland can modulate prolactin secretion by acting through a dopamine mechanism independent of hypothalamic suprachiasmatic structures.The authors thank Ms Karen Shashok for revising the English style. This work was supported in part by a grant GG85-0168 from the Comisión Asesora de Investigación Cientifica y Ténica. The NIAMDD, through the National Pituitary Agency, supplied the radioimmunoassay materials for prolactin determinations.     

Colon absorption of water and NaCl in the rat during lactation and the possible involvement of prolactin

Summary The absorption of water and NaCl by the ascending colon of female rats was significantly increased by prolactin treatment in virgin rats and during suckled lactation. Bromocriptine treatment of lactating rats resulted in decreased colonic absorption, suggesting that increased prolactin secretion may be responsible for the enhanced colonic absorption seen during lactation.This study was aided by NIH/Fogarty Fellowship F 05 TWO 2738 and by NSF Grant PCM-78-10348 to Professor H.A. Bern.The author is greatly indebted to Professor H. A. Bern for his support and helpful suggestions. Ovine prolactin was generously provided by NIAMDD. Professor E. Flückiger, Sandoz Ltd., kindly provided the bromocriptine used in this study. The assistance of William J. Young in taking care of the animals is greatly appreciated.     

Regulation of estrogen "receptors" in mammary tumors: action of prolactin in vivo

The effect of prolactin on estradiol receptors was determined in cytosol of estrogen-dependent mammary tumors of Sprague Dawley rats. Tumors were induced with 20 mg dimethylbenzanthracene, rats were ovariectomized, and the rats showing regression in tumor weight were given 1 mg sheep or rat prolactin for 5 days. Receptors were separated by dextran-charcoal and analyzed by sucrose gradient. Prolactin, milk proteins, serum proteins, and 1-alpha-feto-proteins were excluded immunologically. The estradiol receptors resembled uterine receptors in affinity, specificity, sedimentation, and nuclear transfer under estradiol influence. Castration diminished receptor content exponentially 170 f moles to 16 f moles/mg protein within 10 days; prolactin increased the number of receptors to 87 f moles compared with 15 in controls. Affinity, cellular location, and uterine receptor content were unaffected. Sheep and rat prolactin acted similarly. These results justify hypophysectomy as therapy for certain estrogen-dependent breast tumors.     

Lesions in suprachiasmatic nuclei simulate effects of pinealectomy on prolactin release in ovariectomized and sulpiride-treated female rats

Previous studies indicate that the pineal gland alters prolactin secretion, and it was suggested that at least part of the effect of the pineal hormone melatonin on prolactin release may be mediated by the hypothalamic structures. In this study, pinealectomy and lesions of the suprachiasmatic nuclei were found to alter serum levels of prolactin in the same direction, an effect that was counteracted by daily afternoon melatonin administration. Melatonin, but not other pineal indoles, also prevented sulpiride-induced prolactin secretion in pinealectomized or suprachiasmatic nuclei-lesioned and ovariectomized rats, which suggested that the pineal gland can modulate prolactin secretion by acting through a dopamine mechanism independent of hypothalamic suprachiasmatic structures.     

Regulation of B and T cell development by anterior pituitary hormones

Hormones produced by the anterior pituitary gland have been implicated in the regulation of primary lymphocyte development. In order to identify endocrine factors involved in that process, several strains of mice with genetic defects resulting in a selective impairment in the production of one or more anterior pituitary-derived hormones have been analysed. This study has resulted in the classification of endocrine hormones into the following four categories (i) hormones such as prolactin with no apparent effects on primary lymphopoiesis; (ii) anabolic hormones such as growth hormone and insulin-like growth factor-I whose stimulatory effects on primary lymphopoiesis are non-lineage-specific and related to their actions as systemic mediators of growth and/or differentiation; (iii) hormones such as thyroid hormones that have an obligate role in primary B lymphopoiesis; and (iv) hormones such as oestrogens that act as negative regulators of lymphopoiesis.     

Bombesin-like immunoreactivity in the pituitary gland

Bombesin has been shown to stimulate release of anterior pituitary hormones both in vivo and in vitro. The aim of this study was to determine whether bombesin-like immunoreactivity could be detected in the human pituitary. Significant concentrations were found in the human anterior gland (4.6 +/- 1.5 pmoles/g), posterior gland (1.5 +/- 0.4 pmoles/g) and stalk (8.1 +/- 0.8 pmoles/g). Significant amounts were also observed in the guinea-pig pituitary. Gel permeation chromatography revealed the presence of 2 major molecular forms of bombesin-like immunoreactivity, one co-eluting with porcine gastrin-releasing peptide and the other with amphibian bombesin.     

Zum Einfluss von Angiotensin II auf die Nebennierenrinde unter chemischer adrenostase mit SU 4885 (Metopiron)

Summary The inhibition of 11--hydroxylase in the adrenal cortex with SU 4885 (metopiron) increases the ACTH-secretion. Val₅-angiotensin II blocks the reaction of the anterior pituitary gland similarly as does dexamethasone. Mode and intensity of this action of angiotensin II, and the influence on rats treated as described, are studied.