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Influence of anaesthetics on basal, perphenazine-induced and thyrotrophin releasing hormone-induced prolactin secretion in ovariectomized, oestrogen-treated rats.

Plasma levels of prolactin were determined, by radioimmunoassay, in ovariectomized, oestrogen-treated rats after administration of ether, sodium pentobarbitone, urethane, chloral hydrate or ketamine. These anaesthetics, when administered alone, induced sustained increases in the plasma level of prolactin (continuous ether inhalation), no change in prolactin secretion (urethane), or depressions in the level of prolactin (sodium pentobarbitone, chloral hydrate and ketamine). These same anaesthetics when given before perphenazine failed to alter the stimulatory effect of this phenothiazide on prolactin secretion. Sodium pentobarbitone did not alter the normal increase in prolactin concentration after intra-arterial administration of synthetic thyrotrophin releasing hormone (TRH). These results indicated that anaesthetics do not affect the response of either the central nervous system or the anterior pituitary to perphenazine or TRH although they affect prolactin secretion when administered alone. The site of action of anaesthetics must, therefore, be different from that of perphenazine or perphenazine must be capable of overcoming their influence by direct action on the pituitary.

Anesthetics↗

Effect of synthetic thyrotrophin releasing factor on prolactin and luteinizing hormone secretion in male and female rats during various reproductive states.

The effect of synthetic thyrotrophin releasing factor (TRF) on serum prolactin and LH concentrations was determined by radioimmunoassay in male, cyclic and pseudopregnant female rats. A solution of TRF (0-1, 0-25, 0-5 and 1 mug/rat) was injected i.v. at 17.00 h into rats pretreated with sodium pentobarbitone at 13.00 h. A group of male rats was also treated with TRF at 11.00 h after pretreatment with sodium pentobarbitone at 07.00 h. Fifteen minutes after TRF administration, blood samples were obtained by heart puncture. Doses of 0-25, 0-5 and 1 mug TRF significantly increased the serum prolactin concentration in pro-oestrous rats. The mean serum prolactin level after the injection of 0-5 and 1 mug into oestrous rats and 0-5 mug TRF into dioestrous day 2 rats, was significantly greater than the control values. Injection of TRF on day 1 of dioestrus had no effect. Serum LH concentration was not significantly modified by the various doses of TRF administered. On day 3 of pseudopregnancy a significant increase of serum prolactin values was obtained with 0-5 and 1 mug TRF. On day 7 of pseudopregnancy a dose of 0-5 mug produced the same effect, but on day 10 of pseudopregnancy only 1 mug TRF significantly increased serum prolactin levels when compared with the control rats. In male rats serum prolactin concentration was significantly greater than the control values after TRF treatment either in the morning or the afternoon. The response was similar to that obtained in pro-oestrous rats. The results suggest that the ability of synthetic TRF to stimulate prolactin release exists in both female and male rats and that TRF does not affect LH secretion.

Animals↗

Prolactin, diuretics and urinary electrolytes in normal subjects.

The relationship of plasma prolactin concentration and renal electrolyte excretion has been investigated in six normal male volunteers. In two studies, 80 mg frusemide were administered at 18.00 h on Day 1 and followed by dietary sodium restriction. In study A, after 38 h of sodium depletion, a second dose of frusemide was administered at 08.00 h on Day 3. In study B, after 14 h of sodium depletion, the effect of administration of 100 mg spironolactone or 45 mg prorenoate potassium (another aldosterone antagonist) at 08.00 h on Day 2 was compared with that of a placebo. After the first dose of frusemide in study A, the mean plasma prolactin concentration correlated negatively with the urinary Na and K excretion over 5 h. After 38 h sodium depletion, the plasma prolactin concentration correlated positively with urinary Na excretion following the second dose of frusemide. In study B, after Na depletion for 14 h the plasma prolactin concentration of 08.00 h on Day 2 had a positive correlation with the 24 h urinary log10 Na:K ratio following placebo administration and had negative correlations with the true urinary log10 Na:K ratio following spironolactone and prorenoate potassium administration. Neither acute Na deprivation nor the administration of single doses of frusemide, spironolactone or proprenoate potassium appeared to affect the normal circadian rhythm of plasma prolactin concentrations which remained constant for each subject throughout the 3 months covered by the investigation. The correlations of plasma prolactin concentration to renal excretion of electrolytes, with no evidence for a negative feedback control mechanism, suggest an indirect relationship between prolactin and renal function.

Adult↗

Plasma concentrations of prolactin and thyrotrophin during suckling in urethane-anaesthetized rats.

Plasma levels of prolactin and TSH were determined by radioimmunoassay in urethaneanaesthetized lactating rats during suckling. Oxytocin release was monitored by recording intramammary pressure. Application of ten pups, 3 h after administration of urethane (1-1 g/kg, i.p.), evoked a parallel rise in prolactin and TSH concentrations which reached a maximum during the 3rd hour of suckling and then declined. Peak hormone concentrations represented a 25-fold increase in prolactin and a ten-fold increase in TSH. Suckling also elicited a pulsatile (every 5-10 min) release of 0-5--1-0 mu. oxytocin. The gradual rise in prolactin and TSH occurred between the 1st and 20th oxytocin pulses. Intravenous injection of thyrotrophin-releasing hormone (TRH) into unsuckled, anaesthetized lactating rats resulted in a 7- to 30-fold increase in TSH concentration, whereas prolactin levels showed no substantial change. These results indicate that suckling releases TSH as well as prolactin in the urethaneanaesthetized rat. However, the absence of prolactin release after injections of TRH makes it unlikely that both endocrine responses are regulated solely by the actions of this one releasing hormone.

Anesthesia↗

Action of rat prolactin on plasma somatomedin levels in the rat and on somatomedin release from perfused rat liver.

Rat prolactin at a concentration of 50 ng/ml perfusion medium stimulated the production of somatomedin-like activity (SLA) from the perfused liver of normal rats. The effect was demonstrable in perfusions performed at 11.00 h in which rat prolactin caused a mean (+/- S.E.M.) increase in the uptake of [35S]sulphate into rat costal cartilage in vitro of 64 +/- 14% in comparison with controls, but at 15.00 h no effect was observed. No effect or rat prolactin on hypophysectomized rat liver was detectable at 11.00 h. Hypophysectomized and sham-operated rats were given five intravenous injections of 50 microgram rat prolactin or a similar volume of hormone solvent at 12 h intervals. Plasma somatomedin activity (SMA) and cartilage metabolism, measured by the uptake of radioactive sulphate and thymidine by costal cartilage in vitro, were similar in hypophysectomized animals given rat prolactin or hormone solvent. Sham-operated rats given rat prolactin showed a significant increase of plasma SMA and cartilage metabolism compared with control animals. The production of SLA by rat liver in response to rat prolactin may be related to the density of specific hepatic lactogenic receptors, since these are absent or present only in low numbers in hypophysectomized animals.

Animals↗

Relationship between the suckling-induced release of oxytocin and prolactin in the urethane-anaesthetized lactating rat.

The effects of changes in the intensity of the suckling stimulus on the reflex release of oxytocin and prolactin were compared in urethane-anaesthetized lactating rats. Mothers which had previously suckled 12 pups (Group 1) showed a graded increase in the amount of oxytocin released during a 3 h suckling test when the number of pups applied to the nipples was increased from six to eight or ten. Mothers which had suckled six pups during their lactation (Group 2) appeared to show a maximum frequency of milk ejection whether six, eight or ten pups were applied to the nipples. The release of prolactin was not elicited from either Group 1 or Group 2 mothers when six pups were applied to their nipples. With eight pups suckling, the Group 1 mothers again showed no evidence of prolactin release. In contrast, the Group 2 mothers showed a significant increase in the level of prolactin in the plasma during the 3 h suckling test. With ten pups suckling the release of prolactin was evident in both groups of mothers, although the response was earlier and more pronounced in Group 2 than Group 1. These results suggest that in the urethane-anaesthetized rat, the threshold for the suckling-induced reflex release of oxytocin is distinct from the threshold for the release of prolactin and that these thresholds are, at least in part, set by the preceding suckling experience of the mothers. In those animals which showed both reflex milk ejection and prolactin release there was a linear relationship between the magnitude of the two endocrine responses.

Animals↗

Effects of ovarian steroids and prolactin on the contractility and sodium pump site density of guinea-pig myometrium.

Ovariectomized guinea-pigs were given a single dose of oestrogen or progestogen or the two steroids combined. Controls were given 0.9% saline. Four days after the injection, myometrial contractility in response to spasmogens was measured isometrically in isolated tissue baths, both before and after incubation in Kreb's solution with or without added prolactin. Further myometrial strips were also incubated with or without prolactin and the density of Na+/K+ ATPase 'pump' sites on the surface of the myometrial cell was estimated by labelling with tritiated ouabain. Incubation with prolactin significantly reduced the contractility of myometrial tissue from guinea-pigs given saline alone, progestogen alone or progestogen plus oestrogen, but not in tissue from animals pretreated with oestrogen. When myometrial strips from animals pretreated with oestrogen or progestogen were incubated without prolactin in the medium, there was a significant increase in the density of pump sites compared with the number in saline-pretreated animals; incubation with prolactin did not further modify this effect. When both steroids were administered together there was a significant increase only when prolactin was present in the incubation medium. There was also a significant increase in the density of pump sites after incubation of myometrium from the control (saline-pretreated) animals in the presence of prolactin.

Animals↗

Relationships between prolactin and follicle-stimulating hormone during early pregnancy and the puerperium.

This investigation studies the relationship between the concentrationss of prolactin and FSH in the serum during pregnancy and the puerperium. A single dose of 5 mg bromocriptine during early pregnancy induced a profound fall in the serum level of prolactin with a substantial rise 20 h later. During the initial reduction in the concentration of prolactin, no alteration was noted in the level of FSH but during the subsequent increase in the prolactin concentration, there was a significant (P less than 0.05) decrease in the concentration of FSH. During week 1 of the puerperium, the concentrations of FSH and prolactin were significantly lower in lactating women than in women who were not breast feeding, but there was no significant difference between the concentration of FSH in women who had suppressed lactation with bromocriptine and in those whose lactation was suppressed by non-hormonal methods. when the concentration of FSH was measured every 10 min during a 30 min breast feed, there was a marked but short-lived rise in the serum concentration of prolactin but no change in the level of FSH. These results suggest that an increase in the serum level of prolactin in pregnancy can have a suppressive effect on the production of FSH. Although acute suckling-induced hyperprolactinaemia in the puerperium has no such effect, the maintenance of lactation in the long term does suppress the concentration of FSH in the serum.

Bromocriptine↗

Ontogeny and control of prolactin receptors in the mammary gland and liver of virgin, pregnant and lactating rats.

Prolactin receptors were identified and partially characterized in the mammary gland of the rat. The binding of 125I-labelled ovine prolactin to a subcellular particulate fraction of rat mammary gland decreased between days 30 and 100 of age. Over the same period, binding to the liver increased and there was a significant negative correlation between prolactin binding in the two tissues. Binding to the mammary gland was low during pregnancy, increased in early lactation and declined after the litters were weaned. Binding to the liver was lower during lactation than during pregnancy or the period after weaning suggesting that tissue-specific factors may operate in the control of this receptor. In virgin rats, prolactin binding by the mammary gland was increased by oestrogen. This effect was blocked by hypophysectomy and partially restored by replacement therapy with prolactin. Hypothyroidism and treatment with progesterone also reduced the response to oestrogen. The maintenance of prolactin binding by the mammary gland of lactating rats depends on the presence of the ovaries and pituitary, thyroid and adrenal glands. Examination of the ratio epithelium: stroma suggests that prolactin acts by increasing the number of epithelial cells in the mammary gland and that thyroid, adrenal and ovarian hormones modulate the number of receptors per cell.

Animals↗

Prolactin release in parent ring doves after brief exposure to their young.

A pigeon crop sac radioreceptor assay was used to measure changes in pituitary prolactin levels in parent ring doves of both sexes on the third day after hatching of their young. After a deprivation of 17 h from the squabs, exposure to a 3-day-old squab for 1 h resulted in a significant decrease in the prolactin content of the pituitary gland as compared with levels obtained in control birds deprived of their young for 18 h. No significant sex differences in prolactin levels were observed in either group. Because exposure to the young also promotes prolactin-induced crop sac growth, it appears probable that the squab-induced decrease in prolactin content of the pituitary gland reflects the release of prolactin into the circulation. Accordingly, the environmental regulation of prolactin secretion in parent ring doves appears similar to that observed in lactating mammals.

Animals↗

Effects of histamine implants in several brain regions on the release of prolactin in conscious adult male rats.

The levels of prolactin in the plasma of conscious male rats were determined at various times after an acute administration of histamine or a histamine releasing agent, compound 48/80, in three brain regions. The brain structures that were examined were, the caudal part of the preoptic area and anterior part of the anterior hypothalamic area (POA-AHA), the arcuate nucleus-ventromedial nucleus region (ARC-VMN) and the medial-basal amygdaloid nucleus of the limbic system (AME). A marked increase in plasma levels of prolactin was observed when implants of histamine were in the POA-AHA region. A more consistent increase was found when 1 microgram histamine was injected in the same region; values of prolactin were about 3.6 times greater than in their controls injected with 0.9% saline. Such increased hormone levels lasted up to 2 h. A similar rise in prolactin level was found when the implants of histamine were located in the ARC-VMN region. When compound 48/80 or empty cannulae were placed in those brain regions that were examined, no changes in plasma levels of prolactin were induced. Both histamine and compound 48/80 elicited a delayed and long-lasting decrease of the high plasma level of prolactin present in rats bearing cannulae in the AME region. The results suggest that in the male rat, histaminergic sites, located in rostral and mediobasal hypothalamus and in the central area of the amygdala, are involved in the mechanisms controlling prolactin secretion.

Amygdala↗

Role of serotonin in the regulation of growth hormone and prolactin secretion in the domestic fowl.

Plasma levels of GH and prolactin were measured by radioimmunoassay in male domestic fowl treated with centrally active agents. p-Chlorophenylalanine (pCPA) did not have an effect on tonic levels of prolactin but led to a significant rise in circulating GH concentrations. The three serotonin receptor antagonists tested, methysergide, SQ-10631 and cyproheptadine, each resulted in a significant reduction in plasma prolactin while markedly increasing plasma GH levels. Administration of 5-hydroxytryptophan led to a rise in plasma prolactin and a drop in plasma GH levels in untreated birds or in animals pretreated with pCPA. The serotonin receptor agonist, quipazine, resulted in a marked increase in plasma prolactin and a marked reduction in plasma GH concentrations in untreated birds. In pCPA-pretreated animals quipazine was no longer effective in altering plasma prolactin levels but still caused a significant drop in circulating levels of GH. These results suggest that in the young male domestic fowl serotonin has a stimulatory role in the regulation of prolactin and an inhibitory role in the regulation of GH secretion.

5-Hydroxytryptophan↗

The possible role of prolactin in the regulation of nesting behaviour and the secretion of luteinizing hormone in broody bantams.

The time spent each day on the nest and the rate of formation of the brood patch before the onset of incubation were measured in bantams (Gallus domesticus) and related to changes in the concentrations of plasma LH and prolactin. The hens spent progressively more time on the nest in the 5 days before the onset of incubation so that by the first day of incubation they were spending more than 90% of their time in this way. The concentration of plasma prolactin increased while that of LH fell on successive days before the onset of incubation: the increase in plasma prolactin preceded the fall in plasma LH by 2 days. The formation of the brood patch closely followed the increase in the concentration of plasma prolactin. In four out of five bantams the increase in nesting behavior was preceded by an increase in the secretion of prolactin. An injection of chicken prolactin antiserum into bantams incubating eggs resulted in a significant (P less than 0.05) increase in the plasma concentration of LH. The observations suggest that, in the bantam, the onset of incubation is initiated by an increase in the secretion of prolactin which also suppresses the secretion of LH.

Animals↗

Influence of osmolality and ionic environment on the secretion of prolactin by human decidua in vitro.

The effects of extracellular osmolality and ions on the secretion of prolactin were examined in human decidual explants incubated for 4 h in modified Krebs-Ringer buffer. Explants incubated in media made hypersomotic (280-336 mosM/kg) with sodium, lithium or mannitol or in media made hypo-osmotic (280-224 mosM/kg) by decreasing the sodium concentration secreted the same amount of prolactin as explants incubated in control medium (280 mosM/kg). Explants incubated in calcium-deficient medium secreted 64 +/- 8% (P less than or equal to 0.001) less prolactin than controls (1.65 mmol Ca2+/1). Secretion was restored to control values by the addition of calcium (0.33 mmol/l) or barium (0.5, 1.0 or 2.0 mmol/l) to the medium. Prolactin secretion was unaffected by higher than control extracellular calcium concentrations, calcium ionophore A23187 (10-6, 10-9 mol/l) or lanthanum (0.5, 1.0 or 2.0 mmol/1). Changes in extracellular magnesium (0-20 mmol/l), potassium (0-55 mmol/l) or bicarbonate (0-32 mmol/l) had no effect on prolactin secretion. These results indicate that marked changes in extracellular osmolality and concentrations of sodium, magnesium and bicarbonate have no effects on decidual prolactin secretion. Calcium, however, is essential for the basal secretion of decidual prolactin.

Calcium↗

Gonadotrophin, testosterone and prolactin interrelationships in cadmium-treated rats.

We have investigated the long-term effect of a single subcutaneous injection of cadmium chloride on plasma testosterone and gonadotrophin levels and the prolactin response to the dopaminergic antagonist metoclopramide in the rat. Twelve days after treatment with cadmium there was testicular necrosis, associated with a decrease in testosterone concentration and atrophy of the accessory sexual glands. By 185 days, partial recovery of the accessory sexual glands indicated by Leydig cell regeneration and a slight rise in testosterone levels had occurred. There was, however, persistent damage to the germinal epithelium. Concentrations of LH increased eightfold above controls by day 12, remained raised until 60 days and then decreased to threefold above controls at 280 days. In contrast, FSH levels reached a maximum between 60 and 130 days and remained persistently raised. The peak prolactin response to metoclopramide in cadmium-treated rats was depressed 12 days after cadmium administration and levels remained low at 19 and 75 days. Normal prolactin responses to metoclopramide were obtained 130 days after cadmium treatment using 1:0 mg metoclopramide/kg or 280 days after treatment using 0.25 mg/kg. When control and cadmium-treated rats were castrated at 280 days and then given metoclopramide 10 days later, the prolactin response was significantly reduced. It is concluded that the impaired prolactin response to metoclopramide in cadmium-treated rats is reversible. Prolactin returns to normal in parallel with regeneration of the Leydig cells, partial restoration of the accessory sex organ weight, slight increase in plasma testosterone and decrease in LH levels. These results suggest that testosterone is not solely responsible for the maintenance of normal prolactin secretion in the male rat.

Animals↗

Role of the ovary in the sexual differentiation of prolactin and growth hormone cells in the mouse adenohypophysis: a stereological morphometric study by electron microscopy.

The number of prolactin and growth hormone cells was estimated in the mouse anterior pituitary gland. During postnatal development in females, the number of prolactin cells showed a rectilinear increase from about 0.3 X 10(4) at 20 days of age to about 21 X 10(4) in adult female mice, while growth hormone cells gradually increased from about 7 X 10(4) on day 20 to about 20 X 10(4) on days 60-70, with a plateau level of about 14 X 10(4) cells around puberty. Prolactin cells were more abundant in adult female (about 21 X 10(4)) than in male (about 5 X 10(4)) mice, while there were fewer growth hormone cells in adult females (about 20 X 10(4)) than in males (about 25 X 10(4)). Ovariectomy before puberty induced the male pattern of pituitary development by inhibition of the increase in the number of prolactin cells and stimulation of that of growth hormone cells. In animals ovariectomized just before puberty (30-35 days of age) or 5 days after vaginal opening (40-45 days of age) the number of prolactin cells showed no further increase after the day of operation. On the other hand, when animals were ovariectomized at 10 days of age, the number of prolactin cells increased to the level found in 30-day-old normal control females. This implies that the increase in prolactin cells between 10 and 30 days of age is not dependent on the ovary, although after puberty the increase does depend on the presence of the ovary.

Animals↗

Effects of bromocriptine and naloxone on plasma levels of prolactin, LH and FSH during suckling in the female rat: responses to gonadotrophin releasing hormone.

The roles of dopamine and the endogenous opiate peptides in the mediation of the inverse relationship between prolactin and gonadotrophin secretion during lactation were studied by comparing the effects of bromocriptine and naloxone on plasma levels of prolactin, LH and FSH during suckling in the female rat. The effects of exogenous gonadotrophin releasing hormone (GnRH) on the LH and FSH responses to bromocriptine and naloxone were also assessed. In control animals (saline), there was a marked fall in LH levels and a large increase in prolactin levels within 15 min of suckling. In response to GnRH (25 ng) there was a small progressive increase in LH levels reaching a maximum at 45 min. Both bromocriptine (500 micrograms) and naloxone (500 micrograms) markedly suppressed the suckling-induced prolactin surge when administered in two separate groups of animals. However, despite the bromocriptine-induced suppression of prolactin levels, there was no increase in LH levels which remained low throughout the suckling period. Naloxone (500 micrograms), however, induced a twofold increase in LH levels within 15 min suggesting that an enhanced opiate rather than dopaminergic activity may be responsible for the suppression of GnRH and hence gonadotrophin secretion during suckling. This is supported by the finding that whereas combined bromocriptine (500 micrograms) and GnRH (25 ng) treatment suppressed the suckling-induced prolactin rise and also induced only a small progressive increase in LH (similar to GnRH alone), combined naloxone (500 micrograms) and GnRH (25 ng) treatment induced a sharp sixfold increase in LH levels within 15 min while at the same time markedly suppressing prolactin levels. None of these drug treatments affected the levels of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In-vivo and in-vitro secretion of prolactin by lactating rat adenohypophyses as a function of intracellular age.

Adenohypophysial prolactin of lactating rats was pulse-labelled by [3H]leucine injected i.v. at the time of removal of the pups. The [3H]prolactin concentration in the pituitary gland, analysed by polyacrylamide-gel electrophoresis, progressively fell as the time from labelling to removal of the pituitary gland increased from 8 to 24h, which suggests that there was a loss of hormone as it aged within the gland. Suckling effectively provoked the depletion-transformation of total and [3H]prolactin (extracted at pH 7.2) when applied after 8 h but not when applied after either 16 or 24 h after removing the pups. In rats whose pups were removed for 8 h, suckling also depleted-transformed [3H]prolactin labelled 4 h, but not that labelled 1 h before suckling. The pituitary glands of other lactating rats were labelled with [3H]leucine injected i.v. at various times before removing the glands and incubating them in medium 199. The secretion into the medium of [3H]prolactin labelled either 4, 8, 16 or 24 h beforehand was maximal during the first 30 min then declined from 30 to 240 min of incubation. However, secretion of prolactin labelled 1 h and 10 min beforehand reached a maximum after 0.5-1 h and 2 h of incubation respectively, then remained constant during the remainder of the 4-h incubation period. The total 4-h secretion of [3H]prolactin was greatest (65% of preincubation concentration) from those glands labelled 4 h before in contrast to those labelled 10 min (15%) or 1 (38%), 8 (34%), 16 (18%) or 24 h (26%) before incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗