Rise In Serum Prolactin Research Articles

Stimulation of prolactin secretion in rhesus monkeys by vasoactive intestinal polypeptide.

Vasoactive intestinal polypeptide (VIP) is a potent stimulus for prolactin (PRL) release in rats. The purpose of this study was to test the effect of VIP on PRL secretion in rhesus monkeys and to identify its site of action. Three experimental models were used: (1) intact monkeys during the follicular phase of the menstrual cycle; (2) female, hypophyseal stalk-transected, ovariectomized monkeys (St-OVX), and 93) monkey pituitary tissue perifused in vitro. Initial serum concentrations of immunoreactive PRL were more than 10-fold higher for ST-OVX monkeys (52.4 +/- 10.4 ng/ml, X +/- SEM; n = 6) than for intact monkeys (4. 79 +/- 1.0 ng/ml; n = 10). Intravenous administration of VIP (20 micrograms/kg body weight) induced an elevation of circulating PRL in each of the intact and ST-OVX monkeys tested. On the average, VIP treatment evoked more than a 9-fold rise in serum PRL in intact monkeys (p less than 0.01) and more than a 2-fold increase in ST-OVX monkeys (p less than 0.01), while injection of vehicle alone did not affect PRL levels in either experimental group. Addition of VIP (5 x 10(-9) - 5 x 10 (-6) M) to medium perifusing monkey pituitary tissue in vitro stimulated PRL secretion both in the presence and in the absence of dopamine (2.5 x 10(-6) M). Furthermore, the in vitro potency of VIP was comparable, on a molar basis, with that of thyrotropin releasing hormone. Collectively, these results indicate that VIP is a potent stimulus for PRL secretion in monkeys which exerts its effect, at least in part, by a direct action at the pituitary level. Therefore, VIP should now be considered as a possible PRL releasing factor in primates.

Prolactin responses to histamine H2 receptor antagonists

We have compared the effects of cimetidine and SK&F 92994, a new more potent histamine H2 receptor antagonist, on serum prolactin, and also assessed the effect of the H2 receptor agonist impromidine on the response to cimetidine. As previously reported, cimetidine 200 mg given as an iv bolus dose produced a marked rise in serum prolactin, but 50 mg and 200 mg of SK&F 92994 given by the same route had no effect. Iv infusion of impromidine 10 microgram kg-1h-1 failed to modify the prolactin response to cimetidine. It is concluded that the rise in serum prolactin following iv administration of cimetidine may be due to a specific property of cimetidine. An effect mediated via histaminergic pathways within the central nervous system, although less likely, cannot be excluded.

Effects of p-chlorophenylalanine on the rise in serum prolactin associated with nesting in broody turkeys.

Effects of p-chlorophenylalanine on the rise in serum prolactin associated with nesting in broody turkeys.

The effect of cyproterone acetate on serum testosterone, LH, FSH, and prolactin in male sexual offenders.

The anti-androgen, cyproterone acetate, was administered in a dose of 100 mg/day to eight adult male sexual offenders for 21-31 days. Serum testosterone fell to subnormal levels within 7 days and remained low for 6-28 days after treatment was stopped. The fall in testosterone was accompanied by a fall in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), and a rise in serum prolactin. All subjects experienced a decrease in libido and in frequency of masturbation. The probable mechanisms of action of cyproterone acetate are discussed, as is its potential role in the management of sexual offenders. These studies suggest that measurement of serum testosterone could be used as an index of compliance in sexual offenders treated with cyproterone acetate who are released on parole.

Pituitary microadenoma: diagnostic studies.

Forty-one women with oligo-menorrhoea and/or galactorrhoea were subjected to hypothalamic pituitary-thyroid testing in an attempt to establish the presence or absence of an underlying pituitary microadenoma. They were divided into two groups in accordance with the serum level of prolactin (PRL): Group I (N = 25, mean +/- SE 17.6 +/- 1.5 ng/ml) and Group II (N = 16, 102.8 +/- 29.7 ng/ml). The dynamic tests performed were a TRH test, a stimulation test with metoclopramide (MCP) and a suppression test with bromocriptine. The results of these tests were compared with those obtained in nine normal women and eleven patients with surgically proved pituitary microadenoma. Radiologically abnormal pituitary fossas were found in ten subjects from Group I and in fourteen from Group II. All patients were euthyroid. A persistently elevated serum TSH in response to TRH was observed in patients of Group II suggesting an hypothalamic abnormality and a progressive decrease in the 120-min use of serum T3 was noted with increasing evidence of the existence of a pituitary tumour. A negative correlation was found between the basal serum PRL and the rise of serum PRL with TRH. Patients from Group II showed a lower PRL response to MCP when compared to Group I and again a negative correlation between basal level of serum PRL and the change after MCP was observed. No clear difference in the 4-h response to bromocriptine was found between the different groups of subjects. In conclusion, none of the three tests analysed permitted us to establish which of the patients had an underlying pituitary microadenoma.

Biphasic prolactin release by haloperidol and perphenazine in lactating and pregnant cows and ewes

Single i.m. injections of haloperidol or perphenazine to lactating or non-lactating (pregnant) cows and ewes resulted in bi- or multiphasic elevation of serum prolactin in most of the treated animals, as determined by radioimmunoassay (RIA) up to 16 days after treatment. An immediate rise in serum prolactin occurred 1–4 hr after administration of the drugs, with perphenazine yielding a higher and sharper increase than haloperidol, especially in the non-lactating animals. Sixty-five per cent of the haloperidol-treated, but only 21 per cent of the perphenazine-treated animals, exhibited a second prolactin peak within 3–9 days of treatment, while 15 per cent and 0 per cent, respectively, showed a third peak at an even later stage. These results demonstrate that exhaustion of pituitary prolactin is more profound after perphenazine than following haloperidol. and that the ratios of the first peaks of prolactin to the corresponding basal concentrations are higher in non-lactating than in lactating cows and ewes.

A simple procedure for the assay of brain biogenic amines by selected-ion monitoring: its application to the elucidation of the mechanism of prolactin release induced by 3-iodo-L-tyrosine.

A simple method for the assay of brain biogenic amines by selected-ion monitoring was applied to examination of the effects of 3-iodo-L-tyrosine on the hypothalamic-median eminence concentrations of dopamine, noradrenaline and serotonin in the rat. Thirty minutes after its administration iodotyrosine (50 mg/kg) caused a highly significant (P less than 0.0005) rise in serum prolactin and a highly significant (P less than 0.0025) fall in the concentration of dopamine in the hypothalamus and median eminence where the levels reached 50% of control levels. Less marked but significant falls were also observed in the hypothalamic (P less than 0.05) and median eminence (P less than 0.0025) concentrations of noradrenaline after iodotyrosine administration. Serotonin concentration was significantly reduced (P less than 0.025) in the median eminence but not in the hypothalamus after iodotyrosine administration. These findings suggest that iodotyrosine exerts its prolactin stimulating effect by blockage of dopamine synthesis rather than by receptor blockade.

Effect of the association time of in vivo bound prolactin on the [ 125I]prolactin receptor assays of female rat livers

Significantly ( P < 0.01) reduced 125I-labeled ovine prolactin binding (mean, −22%), as a result of an ether anesthesia-reduced rise in serum prolactin, was observed in plasma membrane preparations of liver samples of female rats taken after 5 min of etherization when compared to samples taken from the same animals during the first minute of etherization. This reduction in assayable receptors occurred after l h but not 2 h of assay incubation time. Significantly ( P < 0.05) reduced 125I-labeled ovine prolactin binding (mean, −16%) was also observed in liver samples exposed to a 30-min ether-induced rise in serum prolactin when compared to liver samples taken during the first minute of etherization. In contrast, this reduction was apparent at assay incubation times of 1, 2 and 4 h but not at 10 h. These results suggest that serum prolactin can bind to prolactin receptors in vivo and partially block subsequent 125I-labeled ovine prolactin receptor assay. In addition, these data provide evidence that a complex time-dependent binding of prolactin may occur in the plasma of the female rat liver.

Effects of testosterone on gonadotrophin responses to synthetic LH and FSH releasing hormone (LRH) in normal men.

LRH tests were performed in 6 adult men with intravenous injections of 25 mug, before and one week after an intramuscular injection of 250 mg testosterone oenanthate (Testoviron Depot). One week after intramuscular injection of Testoviron the tonic secretion of LH was completely suppressed, but the reactivity or the reserve capacity of LH secretion, as tested by LRH, remained unchanged. In contrast, the tonic secretion of FSH and the reactivity of FSH secretion to LRH were both partly suppressed. Three months after the Testoviron injection, the basal levels of LH were still significantly lower than the control values, but the basal levels of FSH were identical to the control values. These data indicate that, in man, the feedback action of testosterone on gonadotrophin secretion could be exerted, at least for LH, at the hypothalamic level rather than at the pituitary level . No significant effects of LRH were noted on the circulating levels of growth hormone and sugar. There was a distinct rise in serum prolactin, which was occasionally significant, within 30 min after LRH injection; this is considered to be without physiological significance.

Ovarian control of prolactin secretion during late pregnancy in the rat.

The involvement of the ovaries during late pregnancy in the rat upon serum prolactin was investigated. Ovariectomy on day 17 or day 21 of pregnancy prevented the dramatic rise of prolactin found in sham-ovariectomized animals between days 21 and 23 of pregnancy. While animals ovariectomized on day 17 of pregnancy failed to carry viable fetuses beyond day 19 of pregnancy, rats ovariectomized on day 21 of pregnancy had viable pups in utero on day 23 of pregnancy. These data suggest that the rise in serum prolactin during late pregnancy is stimulated by ovarian factors.

The stimulation of human prolactin secretion by 3-Iodo-L-tyrosine.

Oral administration of a single 1 g dose of MIT to 10 normal male and female subjects resulted in a rise in serum prolactin in each subject. The mean peak level of serum prolactin attained by the 10 subjects was 36.3 plus or minus 7.9 ng/ml which was highly significantly elevated (P smaller than 0.0005) above the mean basal level of 5.3 plus or minus 1.0 ng/ml. While there was no significant difference between the basal serum prolactin levels of male and female subjects, the mean peak level attained by male subjects following MIT (18.8 plus or minus 3.3 ng/ml) was significantly less (P smaller than 0.0025) than that recorded for the female group (62.5 plus or minus 9.1). Serum levels of growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), triiodothyronine (T3), thyroxine (T4) and cortisol were not significantly altered following MIT administration. The complete absence of side effects due to MIT make it a suitable drug for the acute clinical assessment of pituitary prolactin reserve.

Effect of prostaglandin F 2α on the secretion of human prolactin

Serum prolactin was estimated in 9 women during termination of second trimester pregnancy with prostaglandin F 2α (PGF 2α). Administration of PGF 2α via the transcervical route was associated with a significant increase in serum prolactin. Termination of pregnancy with hypertonic saline or PGF 2α administered intra-amniotically was not associated with a rise in serum prolactin. There was no correlation between the concentration of serum prolactin and the presence or absence of lactation following termination.

Prolactin release and lactogenesis after ovariectomy in pregnant rats: effect of ovarian hormones.

SUMMARY Ovariectomy of rats on day 19 of pregnancy induced a rapid rise in serum prolactin. Levels were significantly increased 4 h after removal of the ovaries and continued to rise up to 24 h. A transient fall occurred at 32 h, but serum prolactin concentration was still raised after 36, 48 and 58 h. Similar increases of serum prolactin occurred after ovariectomy on days 17 and 18 of pregnancy. Lactogenesis occurred 24·8 or 28·2 h after ovariectomy on days 19 or 17–18 of pregnancy respectively. Rats ovariectomized on day 17 or 18 delivered on day 21 and rats ovariectomized on day 19 delivered on day 22 of pregnancy. Ovariectomy impaired parturition in all groups. Treatment with oestrogen immediately after the operation did not prevent the rise in serum prolactin levels 4, 8 and 12 h after ovariectomy, but 24 h after ovariectomy, prolactin values were not significantly different from those in sham-operated control rats. When oestrogen was injected 12 h after ovariectomy, serum prolactin was markedly increased 12 h later. Lactogenesis occurred about 22·9 h after oestrogen treatment and all animals delivered on day 21 of pregnancy. Progesterone treatment prevented the rise in prolactin levels observed 4 and 8 h after ovariectomy, but at 12 h levels had risen and were similar to those observed in untreated ovariectomized rats. Progesterone prevented lactogenesis for 14 h (around 37.5 h after ovariectomy) and induced a delay in the onset of parturition. The results indicate that the decrease of progesterone in the blood after ovariectomy in pregnant rats may induce a release of prolactin and lactogenesis. Oestrogen seems to be effective in raising prolactin levels at low blood concentrations of progesterone.

The inhibitory effect of an ergoline derivative (lergotrile, compound 83636) on prolactin secretion in man.

Compound 83636 (lergotrile), an ergoline derivative, inhibits prolactin release in vitro and in vivo in animals. Studies were designed to evaluate its clinical pharmacologic effects in man. Its chronic administration (2 mg 3 times daily) to normal volunteers and patients results in a decrease in serum prolactin levels. Pretreatment of subjects with single doses of 2, 4, or 6 mg of Compound 83636 delayed the onset of perphenazine-induced elevation of serum prolactin in a dose-dependent fashion. Administration of Compound 83636 (4 or 6 mg) 1 hr after perphenazine administration resulted in a decrease in the elevated serum prolactin levels towards baseline within 15 to 30 min. One week's chronic treatment with Compound 83636 (2 mg 3 times daily) attenuated the expected perphenazineinduced rise in serum prolactin. Compound 83636 appeared to have no significant effect on growth hormone, T3, T4, LH or FSH when compared to determinations made during a placebo control period. It appears that Compound 83636 is a specific inhibitor of prolactin release and may be beneficial in disease states in which lowering serum prolactin is important.

Involvement of neurones containing 5-hydroxytryptamine in the mechanism of prolactin release induced by oestrogen.

SUMMARY Oestradiol benzoate (OB) injected into spayed rats induced high levels of serum prolactin (measured by radioimmunoassay) in the afternoon of the third day after the injection. When progesterone was injected into spayed rats primed 3 days before with OB, a release of prolactin was observed in the morning. These rises in serum prolactin were prevented either by treatment with p-chlorophenylalanine (PCPA), a compound which depletes 5-hydroxytryptamine (5-HT) from the brain or by injecting the 5-HT antagonist methysergide, into the third ventricle. The blockade of prolactin release by PCPA treatment of OB-injected rats was partially reversed by the administration of 5-hydroxytryptophan. These results indicate that 5-HT containing neurones mediate the effect of ovarian steroids on prolactin release. Further support of this view was provided by experiments showing that the injection of 5-HT into the third ventricle raised serum prolactin levels. The rise in serum prolactin observed after the ovarian steroid treatment was blocked to a great extent by the injection of picrotoxin or strychnine. Picrotoxin also blocked the rise in serum prolactin induced by the injection of 5-HT into the third ventricle but failed to affect the rise in serum prolactin after i.v. injection of thyrotrophin-releasing hormone or α-methyl-p-tyrosine treatment. The results suggest that an inhibitory neuronal mechanism mediated by 5-HT neurones is involved in the release of prolactin induced by ovarian steroids.

DNA synthesis and the secretion of prolactin and growth hormone by the pituitary gland of the male rat: effects of diethylstilboestrol and 2-bromo-alpha-ergocryptine methanesluphonate.

SUMMARY The effects of 2-bromo-α-ergocryptine methanesulphonate on the response of the pituitary gland of the male rat to diethylstilboestrol dipropionate were studied by radioimmunoassay of prolactin and growth hormone and measurements of DNA synthesis. Given before diethylstilboestrol, 2-bromo-α-ergocryptine prevented the oestrogen-induced rise in serum prolactin and partly inhibited pituitary DNA synthesis. Given on days 4–6 of a 6-day period after a single dose of diethylstilboestrol, 2-bromo-α-ergocryptine rapidly increased pituitary prolactin concentration, diminished serum prolactin, reduced pituitary DNA synthesis and did not affect the growth hormone response to oestrogen.

Oestrogen and progesterone influence on the release of prolactin in ovariectomized rats.

SUMMARY The concentration of prolactin in serum after oestrogen and progesterone injection into spayed rats was measured by radioimmunoassay. After a single injection of 5 μg oestradiol benzoate (OB) into long-term ovariectomized rats, serum prolactin concentrations showed a circadian rhythm with high levels in the afternoon and almost no changes in the morning. Peaks of prolactin occurred 2, 3 and 4 days after the injection. Below a dose of 1 μg OB, the response was dose-dependent, but the response was then maximal. In spayed rats primed with 5 μg OB, the injection of 2 mg progesterone 2, 3 or 4 days later resulted in a significant increase in serum prolactin. This response, in contrast to that of oestrogen, occurred in the morning and in the evening and was found to be dose-dependent. The rise in serum prolactin after injection of 1 mg progesterone also showed a close relationship to the priming dose of OB. Progesterone had no effect in spayed, untreated animals. Maximal levels of prolactin were attained 3–4 h after the s.c. injection of progesterone. The release of prolactin which can be induced either by OB or by progesterone was blocked by the administration of progesterone injected 1 day before the expected release would occur. These results indicate that progesterone exerts both facilitatory and inhibitory effects on prolactin secretion. Male rats were found to be less sensitive to the ovarian steroid treatment. It is suggested that oestrogen could be responsible for the rise in prolactin observed at pro-oestrus and progesterone for the increase in prolactin in pseudopregnancy and pregnancy.

Evidence that methadone stimulates prolactin release by dopamine receptor blockade.

This study has shown that methadone shares with phenothiazine and butyrophenone neuroleptics the ability to stimulate prolactin release. Administration of D,L-methadone to male rats resulted in elevated serum prolactin levels of a magnitude similar to those noted in rats treated with chlorpromazine or haloperidol. Simultaneous administration of apomorphine and methadone prevented the rise of serum prolactin. We suggest that methadone can stimulate prolactin release by blockading dopamine receptors.

Inhibition of the proestrous surge of prolactin in the rat by nicotine.

Under controlled lighting conditions (14 hr light and 10 hr dark) female rats were injected with nicotine tartrate on the afternoon of proestrus, and periodic measurements were made of their circulating prolactin levels by radioimmunoassay. In rats bled by heart puncture nicotine treatment at 1200, 1400 and 1600 delayed the prolactin surge by at least 90 min. An additional injection of nicotine at 1700 delayed the rise in serum prolactin by at least another 2 hr. A majority of these rats ovulated that night. Extended studies employed intra—atrial cannulas, inserted on the morning of proestrus, through which successive blood samples could be withdrawn from the same animals without anesthesia. Under these conditions peaks of similar amplitude in plasma prolactin were observed at 1800, 1930 and 2130, respectively, in controls and rats treated with 3 and 4 injections of nicotine. The plasma prolactin curves of all 3 groups of rats, destined to ovulate that night, had returned to pre—surge levels by 2300. In similarly treated groups which failed to ovulate there was a brief rise in plasma prolactin starting at 2000 and peaking at 2100 at less than half the elevation attained by the ovulating rats. The close parallelism of the effects of nicotine on the proestrous surges of prolactin and LH emphasizes that there are common elements in the neuroendocrine mechanisms controlling the release of these 2 gonadotropins. (Endocrinology92: 1334, 1973)

Induction and maintenance of pregnancy without rise in serum prolactin in rats.

Induction and maintenance of pregnancy without rise in serum prolactin in rats.