Reduced Prolactin Secretion Research Articles

Hypothyroidism may account for reduced prolactin secretion in lactating rats bearing paraventricular area lesions.

Lesions in the paraventricular area (PVA) of lactating rats have been found to inhibit PRL release. We have examined whether this reduced PRL release is due to hypothyroidism resulting from destruction of the PVA. Rats were made hypothyroid by thyroidectomy on day 15 of pregnancy or by methimazole treatment from the day of parturition. Electrolytic lesions were placed bilaterally in the PVA on day 15 of pregnancy. The following variables were studied: weight gain of the pups, nursing behavior, thyroid status, and release of PRL. The treatments did not affect the time the mothers spent with the pups but reduced the daily weight gain of the pups. Rats with PVA lesions had reduced PRL and TSH levels during lactation compared with controls. Suckling-induced PRL release after 6 h of separation of mothers and pups was less in PVA-lesioned rats than in controls, but T4-treatment did overcome this blunted response in rats with lesions. Levels of T3 and T4 in PVA-lesioned rats were lower than those in controls. In rats made hypothyroid by thyroidectomy or treatment with methimazole, PRL levels were lower and TSH levels higher than those in euthyroid mothers on days 8, 15, and 22 of lactation. Suckling after 6 h of separation of pups and mothers raised PRL levels both in control and methimazole-treated rats, but in the latter animals the response was blunted. It is suggested that the reduced PRL release in lactating rats with PVA lesions could be due to hypothyroidism resulting from these lesions.

Pure uptake blockers of dopamine can reduce prolactin secretion: Studies with diclofensine

The effects of diclofensine, a pure dopamine (DA) uptake inhibitor on 1) 3H-DA uptake in rat arcuate-periventricular nucleus-median eminence synaptosomes, 2) basal and K+-evoked endogenous DA release from tuberoinfundibular dopaminergic (TIDA) neurons and 3) in vivo prolactin (PRL) secretion were studied. Diclofensine, in concentrations of 0.01, 0.1 and 1 μM caused a marked decrease of 3H-DA uptake. In addition, it was unable to stimulate basal endogenous DA release which, on the contrary, was elicited by d-amphetamine in the same concentration (50 μM). On the other hand, diclofensine (50 μM) caused a 3 fold enhancement of K+-evoked DA release. Finally, the compound, when administered in vivo to male rats, significantly reduced basal serum PRL levels. The results of the present study seem to indicate that the pharmacological blockade of DA uptake in TIDA neurons is a condition sufficient to cause a reduction of PRL release.

Nesting Success in Mallards after Partial Clutch Loss by Predators

After partial clutch loss due to predation plasma levels of prolactin, in mallards (Anas platyrhynchos) from a captive flock, decreased significantly from 26 to 11 ng/ml. These ducks also had a reduced hatching success of the remaining clutch. When clutches were experimentally reduced, decreases in plasma concentrations of prolactin were not observed and hatching success was normal. The extended period of reduced prolactin secretion, which follows partial clutch loss by a predator, probably leads to a deterioration in the quality of the incubation patch, which is prolactin dependent, and hence an inadequate heat and moisture transfer to the clutch with subsequent embryonic death. J. WILDL. MANAGE. 51(3):530-533 Disturbance at the nest site of waterfowl usually leads to decreased nesting success (Balat 1969, G6tmark and Ahlund 1984). Under natural conditions a primary cause of reduced nesting success is predation although other causes, such as human disturbance and temporary adverse environmental conditions, may be important (Kury and Gochfeld 1975, Bunnel et al. 1981). When nests of eiders (Somateria mollissima dresseri) with normal clutches are partially plundered by a predator the hatching success (of those birds that do not abandon) is reduced (Choate 1967). Increases in duck nesting success also have been reported when predation was temporarily reduced (Duebbert and Lokemoen 1980). The reason for the decrease in hatching success of the remaining eggs after partial predation, however, was not disclosed by these studies. Since a basic concept of wildlife management is the manipulation of factors that influence the inherent rate of increase of game populations, it is important to know the reason for the reduced nesting success of ducks if production rates are to be maximized. Incubation is a complex behavioral and physiological event in the breeding cycle of birds (Drent 1975). Prolactin has been demonstrated to be intimately involved in incubation of many birds, including waterfowl (Goldsmith and Williams 1980; Dittami 1981; Goldsmith 1982; Bluhm et al. 1983a,b; Hall and Goldsmith 1983). Although the exact role of prolactin has not been fully elucidated, it is believed to be absolutely essential for certain aspects of incubation, especially incubation patch formation and maintenance (Ensor 1978, Goldsmith 1983). Monitori g of plasma prolactin titers may provide a valuable indicator of likely success of incubation. H rein I report on a possible endocrinological mechanism responsible for the observed decrease in nesting success of ducks whose nests have been partially plundered by predators. I am grateful for assistance during the study or manuscript preparation given by H. Buhrow, J. P. Dittami, B. M. Knauer, D. S. Limberger, and J. A. Wozniak. A. S. McNeilly supplied the prolactin antiserum and the Natl. Inst. Health, Bethesd , Md. supplied the prolactin (NIHP-S-12) for use in the radioimmunoassay. MATERIALS AND METHODS Call ucks, a domesticated breed of an ancestral stock of wild mallards, were used in this study. This breed is similar to the mallard in size and time of breeding, molt, and behavior. The birds were kept as pairs in outdoor pens, approximately 6 x 6 x 2 m, that contained a pool (6 x 4 m) and a wooden nest box with straw for nesting material. Experiments were conducted at Seewiesen, West Germany (480N, 11PE) during 2 breeding seasons, 1980 (30 pairs) and 1982 (45 pairs), from late February to midJune. The pens were visited at least once a day. Females were considered to be incubating if they were in the nest box for >2 consecutive days, had stopped egg laying, and had lined the nest cup with down. All ducks used in this study were accustomed to human handling and also were used in a study on the endocrinological basis of incubation (Hall and Goldsmith 1983). Every 1-4 days during egg laying, incubation, and post-incubation the females were captured ' Present address: Department of Zoology, The University, Bristol BS8 1UG, England.

Temporal changes in medial basal hypothalamic catecholamines in male Syrian hamsters exposed to short photoperiod

The gonadal and accessory organ atrophy following transfer of male hamsters from long (LP) to short photoperiod (SP) is preceded by reduced prolactin secretion and involves reductions in hypothalamic LHRH release and catecholamine turnover. These experiments examined the temporal aspects of changes in medial basal hypothalamic/median eminence (MBH/ME) catecholamine turnover rates in male hamsters undergoing SP-induced gonadal atrophy. Hamsters were sacrificed at three, six, nine and twelve weeks of SP exposure. MBH/ME catecholamines and indoleamines were determined by high performance liquid chromatography coupled with electrochemical detection. Reductions in serum prolactin (PRL) levels and increased MBH/ME dopamine (DA) turnover rates were observed at three and six weeks of SP exposure. Both steady state concentrations and turnover rates of norepinephrine (NE) and DA were depressed after nine and twelve weeks of SP exposure, at which time testicular and accessory organ atrophy had occurred. Serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) concentrations were insignificantly changed during the period of SP treatment but the 5-HIAA/5-HT ratio was significantly increased after six weeks of SP exposure. It was concluded that increased MBH/ME DA turnover represents an initial, SP-induced neuroendocrine event. This increase in DA turnover probably contributes to the reduced PRL secretion which precedes, and may play a role in the ensuing gonadal and accessory organ atrophy.

Variation Among Species in the Endocrine Control of Mammary Growth and Function: The Roles of Prolactin, Growth Hormone, and Placental Lactogen

Prolactin, growth hormone, and placental lactogen form a family of structurally related hormones, which may have evolved from a common ancestral peptide. Prolactin and growth hormone are present in all mammals, but the biological activity associated with placental lactogen has been detected in only some groups. Attempts to detect placental lactogen using bioassay and radioreceptor assay are reported and have been unsuccessful in an insectivore (the shrew), a bat, an edentate (the armadillo), a lagomorph (the rabbit), several carnivores (dog, cat, ferret), perissodactyls (horse, zebra, rhino), and, within the artiodactyls, pigs. Placental lactogenic activity has been detected in primates (chimpanzee, orangutan), rodents (voles, Pinon mouse, guinea-pig, mara), and in numerous artiodactyls (llama, giraffe, several species of deer, antelope, gnu, gazelle, musk ox, cape buffalo, Barbary sheep, several sheep of the genus Ovis, goat, and cow). These results confirm and extend the work of others and are discussed in relation to the evolution of these hormones. Insynergism with steroid and thyroid hormones, protein hormones of the prolactin and growth hormone family play a crucial role in stimulating the development of the mammary gland, the differentiation and function of mammary cells to secrete milk, and in the systemic adjustments in maternal metabolism in pregnancy and lactation. Studies in vitro have shown that mammary tissues from several species synthesize milk components in response to insulin plus adrenal corticoid plus prolactin. However, there are also species differences in minimal hormonal requirements for lactogenesis. In vivo, for example, rabbits will initiate or sustain lactation in response to prolactin alone, whereas sheep and goats require prolactin plus growth hormone plus adrenal corticoid plus thyroid hormone. Measurement of hormone concentrations in the plasma of pregnant animals shows considerable differences among species in the pattern of secretion of lactogenic hormones to bring about mammary development. A surge of prolactin secretion occurs at parturition but may not be essential in the initiation of lactation. The timing of progesterone withdrawal correlates well with lactogenesis in eutherian mammals, but species differ in the mechanisms at parturition which bring this about. Marsupials show a quite different pattern of suckling-induced lactation. In maintaining lactation the greatest contrast is between ruminants, in which growth hormone is of particular importance, and other mammals, in which reduction of prolactin secretion with bromocriptine rapidly supresses milk synthesis and secretion. Factors acting locally within the mammary gland, and still largely unidentified, are also important.It is suggested that the requirement to integrate the endocrine control of lactation with other aspects of reproduction may have provided some, at least, of the selection pressures leading to the adoption of different endocrine strategies.

3 Clinical, endocrinological and biochemical effects of zinc deficiency

The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal disease, certain diuretics, the use of chelating agents such as penicillamine for Wilson's disease, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during the growing age period. The clinical manifestations in severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and in man. Inasmuch as zinc is needed for protein and DNA synthesis and cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level and the hypothalamic--pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in a cell division, its deficiency may adversely affect testicular size and thus its function. In mice, the incidence of degenerate oocytes, and hypohaploidy and hyperhaploidy in metaphase II oocytes were increased due to zinc deficiency. Zinc at physiological concentrations reduced prolactin secretion from the pituitary in vitro and it has been suggested that this trace element may have a role in the in vivo regulation of prolactin release. Thymopoietin, a hormone needed for T-cell maturation, has also been shown to be zinc dependent. It is clear that zinc may have several roles in biochemical and hormonal functions of various endocrine organs. Future research in this area is very much needed.

Failure of nomifensine to reduce serum prolactin levels in patients with hepatic encephalopathy.

In order to investigate whether the variations in prolactin (PRL) secretion found in patients with liver cirrhosis are related to the derangement of neurotransmitter metabolism, serum PRL levels were measured in 8 patients with hepatic encephalopathy (a condition where neurotransmission is severely deranged), in 10 patients with liver cirrhosis but without encephalopathy and in 10 control subjects under control conditions and in response to nomifensine, levodopa and synthetic TRH administration. Inhibition of endogenous catecholamine reuptake by nomifensine was able to significantly reduce PRL levels in normal subjects and in patients with liver cirrhosis, whereas only one out of 8 patients with hepatic encephalopathy showed a reduction in PRL levels. On the contrary, levodopa administration was able to reduce PRL secretion in all the subjects studied. PRL release by TRH was greater in patients with liver disease than in controls. The results seem to indicate that the derangement in neurotransmitter metabolism which occurs in liver cirrhosis is one, but not the sole cause of alterations of PRL secretion in liver cirrhosis. The failure of nomifensine to depress PRL is an early finding in the course of encephalopathy and may be of diagnostic value.

Advancement of reproductive activity, seasonal reduction in prolactin secretion and seasonal pelage changes in pubertal red deer hinds (Cervus elaphus) subjected to artificially shortened daily photoperiod or daily melatonin treatments.

Prepubertal red deer hinds were subjected to shortened daily photoperiod (8 h light per day, N = 3) or a daily (afternoon) melatonin injection (N = 4) for 83 days starting on 8 January, 2 weeks after the summer solstice. Compared with control hinds (N = 3) these treatments caused premature moulting of summer pelage, reduced serum prolactin concentrations to barely detectable levels about 34 days earlier than usual and advanced the date of mating. Calves were born earlier (P less than 0.005) in the hinds exposed to a shortened photoperiod (12 November +/- 1.7 days) and melatonin treatment (11 November +/- 3.2 days) than in control hinds (13 December +/- 7.9 days). Serum progesterone levels recorded before the first detected oestrus indicated that silent ovulations had occurred in many of the hinds (6 of 10) in this experiment. This study demonstrated the role of shortened daily photoperiod in red deer and indicated that the effects of reduced photoperiod observed were mediated by melatonin.

Catecholamines and Pituitary Function

Previous studies in Rhesus monkeys have demonstrated that a dopamine (DA) infusion rate of 0.1 microgram/kg X min induces peripheral DA levels similar to those measured in hypophysial stalk blood and normalizes serum prolactin (PRL) levels in stalk-transected animals. We therefore examined the effect of such DA infusion rate on basal and thyrotropin-releasing hormone (TRH)-stimulated PRL secretion in both normal cycling women and women with pathological hyperprolactinemia. 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment. Furthermore, DA significantly reduced, but did not abolish, the rise in serum PRL concentrations induced by both acute 500 mg AMPT administration and 200 micrograms intravenous TRH injection in normal women. A significant reduction in serum PRL levels in response to 0.1 microgram/kg X min DA, similar to that observed in normal cycling women when expressed as a percentage of baseline PRL, was documented in 13 amenorrheic patients with TRH-unresponsive pathological hyperprolactinemia. However, a marked rise was observed in the serum PRL of the same patients when TRH was administered during the course of a 0.1-microgram/kg X min DA infusion. The PRL response to TRH was significantly higher during DA than in basal conditions in hyperprolactinemic patients, irrespective of whether this was expressed as an absolute increase (delta PRL 94.4 +/- 14.2 vs. 17.8 +/- 14.1 ng/ml, p less than 0.002) or a percent increase (delta% PRL 155.4 +/- 18.9 vs. 17.9 +/- 7.1, p less than 0.0005), and there was a significant linear correlation between the PRL decrements induced by DA and the subsequent PRL responses to TRH. These data would seem to show that the 0.1-microgram/kg X min DA infusion rate reduces basal PRL secretion and blunts, but does not abolish, the PRL response to both TRH and acute AMPT administration. The strong reduction in PRL secretion and the restoration of the PRL response to TRH by 0.1 microgram/kg X min DA infusion in high majority of hyperprolactinemic patients, seem to indicate that both PRL hypersecretion and abnormal PRL response to TRH in women with pathological hyperprolactinemia are due to a relative DA deficiency at the DA receptor site of the pituitary lactotrophs.

Effects of external Mg 2+ and Ca 2+ on branchial osmotic water permeabiligy and prolactin secretion in the teleost fish Sarotherodon mossambicus

In Sarotherodon mossambicus prolactin cell activity is related to ambient Ca 2+ levels, and prolactin has hypercalcemic activity in this species. To study whether prolactin has a direct action on calcium metabolism, or whether prolactin's relationship with calcium is indirect and connected with control of gill permeability, the effects of external Ca 2+ and Mg 2+ on prolactin secretion and gill permeability were compared. It appeared that high external Mg 2+ was associated with reduced prolactin secretion, even though high Mg 2+ resulted in a marked hypocalcemia. Exposure of fish to high Ca 2+ levels led to hypercalcemia. Both high Mg 2+ and high Ca 2+ concentrations in the ambient water reduced the osmotic water permeability of the gills. These results represent further evidence that prolactin secretion in S. mossambicus may be affected by any external factor that interferes with branchial permeability. It is concluded that prolactin's main function in this species is connected with control of branchial permeability rather than calcium metabolism, although internal calcium may be implicated in permeability control.

2-hydroxyoestradiol inhibits prolactin release from the superfused rat pituitary gland.

The effects of 2-hydroxyoestradiol (2OH-OE2), dopamine, oestradiol-17 beta and 2OH-OE2 plus dopamine on prolactin and LH release from the male rat pituitary gland were examined in vitro. 2-Hydroxyoestradiol reduced prolactin secretion by 51% at 10(-10) mol/l and by 34% at 10(-7) mol/l, while oestradiol-17 beta had no effect at these doses. Dopamine alone (5 x 10(-7) mol/l) decreased prolactin released by 58%, 2OH-OE2 plus dopamine produced a similar inhibition of 60%. No significant effect on LH release was observed throughout.

Inhibition of prolactin secretion by ergolines.

Peptide-containing ergot alkaloids and synthetic ergoline derivatives were administered to reserpine-treated male rats in order to evaluate their prolactin-inhibiting properties. Each compound was administered ip at a standard 50 ¼g/kg dose. The 9,10-dihydrogenated ergots, dihydroergocornine, and dihydroergocryptine were able to inhibit prolactin to the same degree as ergocornine and ergocryptine. This is significant because the 9,10-dihydrogenation process removes the toxic vasoconstrictive properties from the molecule and allows the prolactin-inhibiting ability to remain intact. In addition, dose-response studies show that minute amounts of an ergot can cause a significant reduction in prolactin secretion. The failure of ergocorninine to inhibit prolactin secretion demonstrates that the stereochemical configuration of the molecule at the 8 position is important for prolactin-inhibiting ability. Interestingly, a number of simple ergot molecules lacking the peptide side chain are able to inhibit prolactin secretion. Substitution at the 1 or 2 position as well as hydrogenation of the indole reduces the prolactin-inhibiting activity. The most active compound is D6-methyl-8βergolineacetonitrile. The high prolactin-inhibiting potency of these compounds suggests that they are able to mimic prolactin-inhibiting factor (PIF). (Endocrinology94: 1171, 1974)

Mechanism of action of prolactin-inhibiting factor.

The effect of rat hypothalamic extract (HE) on prolactin secretion by rat anterior pituitaries in vitro was studied to investigate the mode of action of the prolactin-inhibiting factor (PIF). Explants were incubated for 4 h at 37 ° C in a humidified atmosphere of 5 % CO₂ in O₂ in medium 199 or Earle’s saline. Prolactin in the medium was measured by disc electrophoresis and densitometry. Theophylline (6.7 mM) stimulated prolactin secretion by 50 % and GH secretion by 70%. Elevated potassium (54 mM) increased prolactin release from 16–39%. In low-calcium medium, theophylline restored the reduced prolactin secretion to control levels and increased growth hormone release by 40%. Rat HE inhibited secretion by 30–40% in 1.8 mM calcium medium, but it did not further inhibit the reduced release caused by incubation in low-calcium medium. Elevation of calcium 5–10 times over the 1.8 mM controls did not overcome PIF action. The adenohypophysial explants incubated in medium containing both HE and theophylline secreted as much prolactin as those incubated in control medium. It thus appeared that theophylline nullified PIF action. However, in comparison with the incubates with theophylline alone, in which prolactin secretion was stimulated over control levels, the HE had as much PIF activity in the presence of this methylxanthine as it did in its absence. Elevated potassium also overcame HE inhibition of prolactin release. However, prolactin release by pituitaries incubated with high K⁺ plus HE was only slightly lower than that of glands incubated with high K⁺ alone. Thus, PIF can be fully active in the presence of theophylline, but not in elevated K⁺. This suggests that high K⁺ and PIF act on the same process and theophylline influences secretion by a different mechanism. The results show that the inhibitory action of PIF is manifested only when sufficient extracellular calcium is present to support spontaneous secretion of prolactin. In addition, they suggest that PIF exerts a stabilizing action upon the plasma membrane of the lactotrope and this prevents calcium entry and initiation of prolactin release.