Reduction of body fat stores by inhibition of prolactin secretion

Reductions of prolactin secretion by bromocriptine treatment for 24 days reduced fat stores (abdominal and epididymal fat depots) in hamsters by 25-49% compared with control animals. However, body weights and food consumption were not affected. These results further substantiate an important role for prolactin in regulation of fat metabolism and indicate that bromocriptine might be used to decrease fat stores.     

Timed bromocriptine administration reduces body fat stores in obese subjects and hyperglycemia in type II diabetics

Obese postmenopausal female volunteers were given timed daily oral dosages of bromocriptine, and tested for reduction of body fat stores. This dopamine agonist has been shown to reset circadian rhythms that are altered in obese animals and to reduce body fat levels in several animal models. The participants were instructed not to alter their existing exercise and eating behavior during treatment. Skinfold measurements were taken on 33 subjects as indices of body fat. The measurements (e.g., suprailiac) were reduced after six weeks by about 25%, which represents a reduction of 11.7% of the total body fat. These dramatic decreases in body fat, which are equivalent to that produced by severe caloric restriction, were accompanied by more modest reductions of body weight (2.5%), indicating a possible conservation of protein that is usually lost as a consequence of such caloric restriction. The effects of bromocriptine treatment on body fat and hyperglycemia were also examined in non-insulin dependent diabetics being treated with oral hypoglycemics (7 subjects) or insulin (7 subjects). Total body fat was reduced by 10.7% and 5.1% in diabetics on oral hypoglycemics and insulin, respectively, without any significant reductions in body weight.Hyperglycemia was reduced in most of the 15 diabetic subjects treated leading to euglycemia and even cessation of hypoglycemic drugs in 3 of the 7 subjects during 4–8 weeks of bromocriptine treatment. These findings support the hypothesis that obesity and type II diabetes may be treated effectively with bromocriptine when administered at the proper times and dosages.This is a process patented by Louisiana State University and licensed to Ergo, Inc., Newport, Rhode island. A. H. Meier and A. H. Cincotta have financial interest in the process.     

Timed bromocriptine administration reduces body fat stores in obese subjects and hyperglycemia in type II diabetics.

Obese postmenopausal female volunteers were given timed daily oral dosages of bromocriptine, and tested for reduction of body fat stores. This dopamine agonist has been shown to reset circadian rhythms that are altered in obese animals and to reduce body fat levels in several animal models. The participants were instructed not to alter their existing exercise and eating behavior during treatment. Skinfold measurements were taken on 33 subjects as indices of body fat. The measurements (e.g., suprailiac) were reduced after six weeks by about 25%, which represents a reduction of 11.7% of the total body fat. These dramatic decreases in body fat, which are equivalent to that produced by severe caloric restriction, were accompanied by more modest reductions of body weight (2.5%), indicating a possible conservation of protein that is usually lost as a consequence of such caloric restriction. The effects of bromocriptine treatment on body fat and hyperglycemia were also examined in non-insulin dependent diabetics being treated with oral hypoglycemics (7 subjects) or insulin (7 subjects). Total body fat was reduced by 10.7% and 5.1% in diabetics on oral hypoglycemics and insulin, respectively, without any significant reductions in body weight. Hyperglycemia was reduced in most of the 15 diabetic subjects treated leading to euglycemia and even cessation of hypoglycemic drugs in 3 of the 7 subjects during 4-8 weeks of bromocriptine treatment. These findings support the hypothesis that obesity and type II diabetes may be treated effectively with bromocriptine when administered at the proper times and dosages.     

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.     

Bromocriptine-induced removal of endoplasmic membranes from prolactinoma cells

Summary Adenomatous prolactin cells lose 39% of their cytoplasm volume within 7 days after the beginning of bromocriptine treatment. A simultaneous reduction of the rough-surfaced endoplasmic reticulum and the Golgi apparatus occurs. Their membranes are removed by rapid transport along the secretory pathway to the cell surface and to lysosomal destruction.We thank Prof. E. del Pozo, Sandoz Ltd, Basle, for the generous gift of injectable bromocriptine, Prof. E.R. Weibel, Dept. of Anatomy, University of Bern, for his technical advice, Dr U. Helfenstein, Institute of Biostatistics, University of Zürich, for his help in the statistical evaluation of the results and the EMDO-Foundation, Zürich, for financial support.     

Neither prolactin nor growth hormone restore the nocturnal rise in pineal N-acetyltransferase activity or melatonin content in hypophysectomized rats

Hypophysectomy in adult male rats greatly attenuated the nocturnal rise in both pineal N-acetyltransferase (NAT) activity and melatonin content. High nighttime levels of NAT and melatonin were not restored by treating the animals with either prolactin or growth hormone, alone or in combination. Treating intact rats with bromocriptine, which depresses circulating prolactin levels, also was without effect on pineal melatonin synthesis. It appears that neither prolactin nor growth hormone are of major importance in determining pineal melatonin production.     

Neither prolactin nor growth hormone restore the nocturnal rise in pineal N-acetyltransferase activity or melatonin content in hypophysectomized rats

Summary Hypophysectomy in adult male rats greatly attenuated the nocturnal rise in both pineal N-acetyltransferase (NAT) activity and melatonin content. High nighttime levels of NAT and melatonin were not restored by treating the animals with either prolactin or growth hormone, alone or in combination. Treating intact rats with bromocriptine, which depresses circulating prolactin levels, also was without effect on pineal melatonin synthesis. It appears that neither prolactin nor growth hormone are of major importance in determining pineal melatonin production.     

Prolactin secretion inhibition by a new 8a-amino-ergoline,CH 29-717

Summary In rats, CH 29-717 inhibits basal and physiologically or chemically stimulated prolactin secretion. It is more potent than the standard bromocriptine.     

Pharmacodynamic profile of CQP 201-403, a novel 8α-amino-ergoline

Summary The profile of action in animals of CQP 201-403, a novel 8-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and to be more potent than bromocriptine (Parlodel^®).In memory of Dr Annemarie Closse, who died 14 June 1987.     

Bromocriptine-induced removal of endoplasmic membranes from prolactinoma cells

Adenomatous prolactin cells lose 39% of their cytoplasm volume within 7 days after the beginning of bromocriptine treatment. A simultaneous reduction of the rough-surfaced endoplasmic reticulum and the Golgi apparatus occurs. Their membranes are removed by rapid transport along the secretory pathway to the cell surface and to lysosomal destruction.     

Does prolactin control the blood progesterone level on early dioestrus in rats?

Summary Bromocriptine treatment on either prooestrus or oestrus in female rats did not affect luteal function on the day of dioestrus 1.This investigation was partially financed by the C.N.R.S. (E.R.A. No. 566).Acknowledgments. We are thankful to Mrs C. Lazarus for her excellent technical assistance, to Mr R. Dujol for the figures. We wish to express our gratitude to Dr A.F. Parlow for providing reagents for prolactin RIA and to Sandoz Laboratories for bromocriptine. Reprint request should be addressed to Cl.A.     

Plasma growth hormone in the rabbit fetus. Relation to maturation of the liver and lung]

Day 25 after insemination is a date of peculiar importance in the maturation of several organs in the Rabbit fetus. From day 25 onward the fetal liver stores increasing amounts of glycogen and the lung stores increasing amounts of lecithins, concomitant with sudden rise in the activity of lung phosphatidic-acid phosphohydrolase. Earlier studies on decapitated fetuses established that glycogen storage in the liver is dependent on a dual hormonal control, comprising a pituitary hormone like growth hormone or prolactin (some placental hormones share the same activity) and corticosteroids (Jost, 1961). Since the variations in endogenous corticosteroids do not seem to herald these liver or lung changes (Mulay et al., 1973), a study was made of growth hormone. Plasma immunoreactive growth hormone--determined with a heterologous Rat system (Kervran et al., 1976)--increases eightfold between days 23 and 25. During the same time plasma prolactin does not change according to McNeily and Friesen, 1978, and to unpublished data obtained with Dr McNeilly. In preliminary assays, Rat growth hormone was seen to increase phosphorylase "a" activity in the lung of 18.5 day-old Rat fetuses, thus anticipating normal development. We suggest that growth hormone plays a role in initiating liver and lung maturation.     

The lack of an effect of cholinergic agonists on anterior pituitary prolactin production in vitro

Summary The addition of dopamine to anterior pituitary incubations resulted in a marked decrease (88% for³H prolactin and 69% for RIA prolactin) in prolactin release. Incubation with the cholinergic agonists carbacol, arecoline and nicotine resulted in no significant change in prolactin secretion.Supported in part by NSF Research grant No. BMS 74-17332.The authors appreciate receiving as a gift from the National Institute of Arthritis, Metabolic and Digestive Diseases, the rat prolactin used for iodination (RP-I₂) and standards (RP-1).     

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.     

Peptide-stimulated release of prolactin from the fowl anterior pituitary gland

Summary Anterior pituitary glands from broiler fowl were preincubated for 24 h in either medium 199 only or medium containing estradiol 17, following which they were incubated in medium containing thyrotrophin releasing hormone (TRH), vasoactive intestinal polypeptide (VIP) or substance P (SP), alone or with the dopamine agonist, apomorphine. Estradiol priming stimulated release of prolactin and enhanced apomorphine-inhibition of prolactin release. TRH stimulated prolactin release, an effect reversed by apomorphine, and priming with estradiol potentiated both effects. VIP stimulated prolactin to a lesser degree and again this was inhibited by apomorphine and potentiated by estradiol. SP had little effect on the nonsteroid-primed pituitary, but stimulated release of prolactin after estradiol treatment, though less effectively than TRH or VIP.     

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.     

Lipid sensing and lipid sensors

Lipid droplets have been considered for a long time as inert intracytoplasmic deposits formed within cells under various conditions. Recently, new tools and new approaches have been used to visualize and study these intracellular structures. This revealed new aspects of lipid droplets biology and pointed out their organized structure and dynamic composition. In adipocytes, the specialized cell type for the storage of energy as fat, lipid droplets are particularly well-developed organelles and exhibit unique properties. Also discussed in this paper is the view that lipid droplets, through specific candidate constituents, can play a role in sensing the level of their lipid stores by adipocytes.     

Influence of dopamine infusion on plasma prolactin released by kidney capsule transplanted anterior pituitaries

Summary The infusion of dopamine into the renal artery resulted in decreased prolactin release from 3 anterior pituitary glands transplanted under the kidney capsule. Prolactin levels continually decreased over a 5 min period after DA infusion was terminated and thereafter approached preinfusion levels by the end of 10 min.Supported by NSF Research, grant No. 74-17332.The authors wish to express their appreciation to Mrs Cynthia Van De Walle for her outstanding technical assistance in the performance of the prolactin RIA and the statistical analyses. We also appreciate receiving as a gift from the National Institute for Arthritis, Metabolism and Digestive Diseases the rat prolactin used for iodination (RP-I₂) and standards (RP-1).     

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.     

The influence of long term estrogen treatment on plasma prolactin levels induced by ether anesthesia in ovariectomized rats

Summary 2 methods of continuous estrogen delivery, polyestradiol phosphate injection and implantation of Silastic capsules of estradiol-17 , in ovariectomized rats induced increases in plasma prolactin in the afternoon (15.00–17.00) beginning at 1 week and continuing for 4–8 weeks. In addition these methods of estrogen treatment potentiated the ether-induced increase in plasma prolactin in the morning (9.00–11.00) beginning on week 2 and continuing for 3–8 weeks. These results indicate that estrogen activates the mechanisms that cause an afternoon surge in prolactin before potentiating a morning elevation induced by ether anesthesia.Acknowledgment. This work was supported by NIH General Research Support, grant No. RR05384-14 to Wayne State University School of Medicine. The authors also with to express their appreciation to Mrs C. Van De Walle for her expert technical assistance in the prolactin radioimmunoassay, to Dr Richard R. Gala for his advice and support of this project and to the Rat Pituitary Hormone Distribution Program of NIAMDD for the generous gift of Rat Prolactin.