Increased Plasma Prolactin Concentrations Research Articles

Transient increase in prolactin secretion following hypothalamo-pituitary disconnection in ewes during anoestrus and the breeding season.

Hypothalamic control of prolactin secretion was studied in ovariectomized ewes by comparing the effects of hypothalamo-pituitary disconnection (HPD) and sham-operation (sham-HPD). HPD caused a two-fold increase in plasma prolactin concentrations on days 1 and 7 following surgery during anoestrus and a tenfold increase during the breeding season. Thereafter, concentrations gradually declined to be similar to those in sham-HPD ewes by day 43 (breeding season) and day 145 (anoestrus). The maximum plasma prolactin response to HPD was similar during the two seasons (anoestrus: 128 +/- 15 bs breeding season: 118 +/- 13 micrograms/l). Sham-HPD had no effect on plasma prolactin concentrations. Prolactin pulse frequency was not affected by HPD, but increases in plasma prolactin concentrations were associated with increases in pulse amplitude. At the time of the normal anoestrus, plasma prolactin concentrations rose in both the HPD and sham-HPD ewes, raising the question of extra-hypothalamic regulation of seasonal changes in prolactin secretion. Plasma LH and FSH concentrations became undetectable in HPD ewes but were unaltered in sham-HPD ewes. We conclude that hypothalamic inhibition of pituitary prolactin secretion in the sheep can be demonstrated by HPD but that this effect is not sustained. This transience may indicate the additional requirement of hypothalamic-releasing factors in the control of prolactin release. In addition, the surgically isolated ovine pituitary of the HPD animal has an inherent pulsatile secretion of prolactin.

Factors affecting prolactin secretion during the breeding cycle of the ring dove (Streptopelia risoria) and its possible role in incubation.

Plasma prolactin began to increase significantly about 5 days after the onset of incubation in both sexes of the dove to reach a peak at the time of hatch. At this time, the concentration of prolactin in the plasma of the female was significantly higher than in the male. In the middle of the incubation period prolactin levels measured over a 24-h period remained constant in both sexes, although the male sits during the middle of the day and the female for the rest of the time. Nest deprivation resulted in a sharp, significant decline in the concentration of prolactin in both sexes. Newly hatched squabs stimulated the release of prolactin only in those doves which had been incubating eggs for several days. A distinct sex difference was observed in the expression of nest defence behaviour of the ring dove during the breeding cycle. At the time of laying, the female was significantly more aggressive than the male and her aggression increased only slightly up to the time of hatching. In contrast, male aggression increased gradually from a low level at laying to reach a peak at the time of hatching. The levels of plasma progesterone in the female showed a significant increase around the time of lay. No significant changes occurred in the plasma concentration of either progesterone or 17 alpha-hydroxyprogesterone in the male. Administration of prolactin increased the length of time of incubation of infertile eggs. Nest manipulations which had the effect of inducing the doves to begin incubation 4 days before laying showed that (1) the length of time of incubation of infertile eggs is fixed and independent of events which occur at courtship or oviposition, (2) the initiation of the increase in plasma prolactin concentration during incubation is independent of events which occur at courtship and oviposition and (3) the termination of incubation is always preceded by a fall in the concentration of plasma prolactin. It is concluded that the length of time of incubation is dependent upon sustained raised levels of plasma prolactin. The concentration of plasma prolactin increases several days after the onset of incubation in response to the tactile stimulation of sitting. High levels, if maintained by visual stimulation from the nest, maintain incubation for a fixed period. After this, if the eggs fail to hatch, prolactin levels fall and the doves cease incubation and begin a new cycle.

Superior cervical ganglionectomy prevents gonadal regression and increased plasma prolactin concentrations induced by long days in goats.

The effects of the abolition of the diurnal change in melatonin secretion on the photoperiodic response of the gonadal axis and prolactin secretion to long days were examined in female goats. Female Saanen goats, reared under short-day conditions (8 h light: 16 h darkness; lights on at 05.00 h) at 22 +/- 2 degrees C for 5 months, were bilaterally superior cervical ganglionectomized (SCGX). One month after surgery, both SCGX and intact control goats were divided into two groups. Animals in group 1 were maintained under short days and those in group 2 moved to long days (16 h light: 8 h darkness; lights on at 05.00 h). In group 1, both SCGX and intact goats ovulated periodically and basal plasma prolactin levels were maintained throughout the day. In intact controls, exposure to long days suppressed ovulation and increased prolactin secretion for the first 150-200 days of exposure. The animals became photorefractory after this time; ovulation recurred and prolactin secretion returned to basal levels. Superior cervical ganglionectomy abolished or weakened the suppression of gonadal function and eliminated the increase in prolactin secretion induced by exposure to long days in the intact controls. These results suggest that the pattern of melatonin secretion under long days is necessary to induce the photoperiodic response of gonadal function and prolactin secretion to long days and that, under natural conditions, melatonin regulates the seasonal changes in gonadal function and prolactin secretion by mediating the effect of long days.

Regulation of testicular LH/hCG receptors in golden hamsters (Mesocricetus auratus) during development.

During prepubertal development in the golden hamster, there are major age-related changes in the number of testicular LH/hCG receptors. Between 22 and 35 days of age, there was greater than 10-fold increase in testicular LH/hCG receptors, followed by a decrease at Day 37. Concomitant with, but preceding slightly, the changes in receptors, were increases in plasma LH and FSH and most noticeably prolactin concentrations, between Days 10 and 20 of age. Inhibition of the increases in plasma levels of prolactin by daily injections of bromocriptine, between 14 and 31 days of age, resulted in suppressed testicular and seminal vesicle weights, and decreased content and concentration of testicular LH/hCG receptors. Similarly, the premature increase in plasma prolactin concentrations in prepubertal hamsters between 6 and 20 days of age, by means of ectopic pituitary transplants, resulted in increased testicular and seminal vesicle weights, as well as an increase in the concentration of testicular LH/hCG receptors. These results strongly suggest that increases in plasma prolactin values during development are important in enhancement of the development of testicular LH/hCG receptors.

Effect of immunoneutralization of thyrotrophin-releasing hormone on the release of thyrotrophin and prolactin during suckling or in response to electrical stimulation of the hypothalamus in the anaesthetized rat.

The aim of the present study was to use the technique of immunoneutralization with anti-thyrotrophin-releasing hormone (anti-TRH) serum to investigate the role of TRH in mediating the TSH and prolactin responses to electrical stimulation of the hypothalamus and the prolactin response to suckling in lactating rats. Electrical stimulation of either the median eminence or paraventricular nuclei of male or female rats anaesthetized with urethane resulted in significant increases in the plasma concentrations of both TSH and prolactin. Injection of sheep anti-TRH serum blocked the rise in plasma TSH concentration in response to stimulation of either brain area, but did not block the increase in plasma prolactin concentration. In anaesthetized, lactating female rats, the suckling stimulus produced a significant increase in the plasma prolactin concentration, but did not alter the plasma TSH concentration. Injection of anti-TRH serum, but not control non-immune or anti-bovine serum albumin, significantly decreased the basal release of TSH but did not abolish the prolactin response to suckling. These results show that TRH is the principal mediator of the neural control of TSH release in the rat, but is not crucial for the release of prolactin in response to either hypothalamic stimulation or suckling.

Endocrine changes in the fowl during infection with Eimeria maxima

Plasma concentrations of thyroxine (T4), triiodothyronine (T3), prolactin, growth hormone and corticosterone were measured in immature domestic fowl which were infected with Eimeria maxima, uninfected but given the same amount of food as those infected (pair-fed) or fed ad libitum. Infection with E maxima caused a decrease in plasma T4 concentration whereas pair feeding caused an increase when food intake was minimal. Plasma T3 concentrations were decreased similarly in both infected and pair-fed birds. Infection caused an increase in plasma prolactin concentration, whereas pair-feeding did not. The plasma concentration of growth hormone was not affected by any of the treatments. Plasma corticosterone concentration was markedly increased on days 5 and 6 in pair-fed birds but was not affected by infection with E maxima.

Effect of propiomazine on plasma prolactin in the rat: counteraction by L-dopa.

A single iv injection of 0.31, 0.62, 1.25, 2.5, 5, 10, or 20 mg/kg body wt of a phenothiazine derivative, propiomazine (PP), into male rats significantly (P less than 0.05) increased plasma prolactin concentrations. The higher doses (5, 10, and 20 mg/kg body wt) produced increases that were greater in both magnitude and duration than those produced by the lower doses. The higher doses of PP, along with the elevations in plasma prolactin, also produced concomitant decreases in plasma luteinizing hormone (LH) levels. Pretreatment with L-dopa (100 mg/kg body wt) completely blocked the PP-induced stimulation of prolactin release, indicating that antidopaminergic action of PP either at the hypothalamic or anterior pituitary level was responsible for its effects on the release of prolactin.

Decreased tuberoinfundibular and pituitary dopamine and dihydroxyphenylacetic acid concentrations in rats with estrogen-induced pituitary tumors

The majority of pituitary adenomas are prolactin (PRL)-secreting, but it is still uncertain whether their pathogenesis results from a central nervous system (CNS) disturbance or autonomous lactotroph growth and function. We have measured dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) concentrations in rats bearing estradiol-induced PRL-secreting pituitary tumors. Female rats, injected at 3-week intervals with 2 mg estradiol valerate (EV), had increased plasma prolactin concentrations, up to 3 micrograms/ml, at 31 weeks. Inversely, there was a reduction of DA and DOPAC in the median eminence and arcuate nucleus as well as a decreased DOPAC/DA ratio in the arcuate nucleus. DA-containing nuclei in the other parts of the brain were not affected. Anterior pituitary weight increased while its DA concentration decreased during estradiol treatment. In the neurohypophysis, DA concentrations were unchanged while DOPAC and the ratio DOPAC/DA decreased following the estrogen treatment. Our data suggest that rats with primary estrogen-induced PRL-secreting tumors have a defect in the CNS-DA neurotransmission.

Serotonergic stimulation of prolactin and corticosterone secretion is mediated by different pathways from the mediobasal hypothalamus.

In previous studies we obtained evidence that serotonin release by p-chloroamphetamine (PCA) causes an increase in corticosterone secretion but that this effect is not mediated via the raphe nuclei in the midbrain. In contrast, PCA-induced prolactin secretion was abolished by dorsal raphe lesions. In the present study, posterolateral cuts which interrupted caudal inputs to the hypothalamus attenuated the effect of PCA on plasma prolactin but did not block the PCA-induced increase in plasma corticosterone levels. Large lesions of the mediobasal hypothalamus produced a significant reduction of plasma corticosterone concentration but did not completely prevent the effect of PCA on corticosterone secretion. Hypophysectomy performed 24 h before sacrifice caused a marked decrease in plasma corticosterone levels but did not completely abolish the effect of PCA. These results suggest that PCA also stimulates corticosterone secretion via a direct action on the adrenal gland. The lesions in the mediobasal hypothalamus caused an increase in plasma prolactin concentration, and in these rats, PCA suppressed rather than stimulated prolactin secretion. This suggests that the known weak dopamine agonist activity of PCA is exposed when the effects of serotonin release in the brain are eliminated.

Bovine neurophysin II has prolactin-releasing activity in the estradiol-primed male rat.

In the course of the search for the prolactin-releasing factor (PRF), we noticed that the posterior pituitary contained strong PRF activity and subsequently traced this activity to that of bovine neurophysin-II (NP-II). NP-II prepared in our lab was judged to be a homogeneous preparation according to Sephadex G-75 gel filtration, DEAE ion exchange chromatography and polyacrylamide gel electrophoresis. While neurophysin-I (NP-I) injections of 100 micrograms/kg and 1,000 micrograms/kg elevated plasma prolactin in estradiol-primed male rats to 30% and 50% over the control value, respectively, NP-II doses of 100, 1,000 micrograms/kg increased plasma prolactin concentration in estradiol-primed male rats to 130% and 170% over the control value, respectively. The lowest dose of NP-II needed to increase plasma prolactin concentration was 10 micrograms/kg. Since neurophysin does not stimulate prolactin release from the ectopic pituitary under the kidney capsule nor from lactotrophs in a primary monolayer culture system, neurophysin is believed to act indirectly on the pituitary, presumably through a neurotransmitter and/or hypothalamic releasing (or inhibiting) factor. We propose that NP-II may be one element in the complex chain of the prolactin-releasing mechanism.

Effect of tamoxifen on growth and prolactin secretion of rat pituitary tumours.

The antioestrogenic drug tamoxifen was administered to rats bearing transplanted prolactin-secreting tumours derived from spontaneously occurring pituitary adenomas in Wistar-Furth rats. Some inhibition of tumour growth was observed but this was accompanied by an increase in plasma prolactin concentrations. Bromocriptine, however, consistently inhibited both growth and prolactin secretion of these tumours. The addition of tamoxifen to bromocriptine treatment produced no increased response to the dopamine agonist. Tamoxifen increased prolactin secretion by tumour cells in vitro but did not affect DNA synthesis. Normal rats responded to tamoxifen with a moderate increase in plasma prolactin concentrations and there was no change in pituitary DNA synthesis.

Cathodal versus anodal stimulation within the preoptic-suprachiasmatic region in male rats: Effects on the release of prolactin and luteinizing hormone

The relative efficiency for the release of luteinizing hormone (LH) and prolactin after anodal and cathodal stimulation applied within the preoptic-suprachiasmatic region (POA-SCH) was studied in adult male rats under pentobarbital anesthesia. Single monopolar pulses 0.5 ms duration, 100 or 200 μA intensity, were applied within the dorsal [vertical (V) 7.3] or ventral (V 7.8 to 7.9) aspects of the POA-SCH at a mean rate of 10 Hz in 30-s trains every other 30 s for a period of 30 min. Blood samples were obtained at 30-min intervals starting immediately before onset of stimulation. Although there was no obvious effect on plasma LH titers, prolactin concentrations tended to be higher when cathodal stimulation was applied at V 7.9 and when anodal pulses were applied at V 7.3. Stimulation with paired twin pulses (1.0 ms duration, 20.0 ms intrapair interval) resulted in clearer hormonal effects, namely, a significant increase in plasma prolactin concentration at 30 min only when cathodal stimuli were applied to the ventral aspect of the POA-SCH. Plasma LH concentrations were higher also at 30 min in the same experimental group, although the increase was not statistically significant. These results indicate the effectiveness of cathodal stimuli to induce hormonal release when applied within the ventral half of the POA-SCH in male rats. Present results suggest the existence of predominantly facilitatory neural elements for the release of prolactin (and LH) in this brain region.

Modulation of corticosteroid secretion by dopaminergic mechanisms in rhesus monkeys.

This study was designed to investigate dopaminergic mechanisms in the control of corticosteroid secretion. Ten rhesus monkeys received metoclopramide (1.25 mg iv) or domperidone (1.25 mg iv) with 5% dextrose (vehicle) or with dopamine (4 micrograms.kg-1.min-1) infusions begun 60 min before administration of the dopamine antagonist. Metoclopramide, in the presence of vehicle, increased plasma 18-hydroxycorticosterone from 11.2 +/- 1.0 ng/dl to a maximum concentration of 50 +/- 5.1, plasma aldosterone from 5.4 +/- 0.7 ng/dl to a maximum of 38.2 +/- 4.9, and prolactin (PRL) concentrations from 8.5 +/- 1.2 ng/ml to a maximum of 114.6 +/- 7.2. Domperidone, in the presence of vehicle, increased plasma PRL concentrations from 8.6 +/- 1.2 ng/ml to a maximum of 148.7 +/- 7.8 but had no effect on plasma corticosteroids. Dopamine infusion inhibited the 18-hydroxycorticosterone, aldosterone, and PRL response to metoclopramide and the PRL response to domperidone. These results demonstrate that 18-hydroxycorticosterone and aldosterone responses to metoclopramide and PRL responses to metoclopramide and domperidone are mediated by their antagonist activity at dopamine receptors. Domperidone may fail to stimulate aldosterone secretion because it does not cross the blood-brain barrier or fails to act as an antagonist at the glomerulosa dopamine receptor through which dopaminergic modulation of corticosteroid secretion is mediated. A parallel time course of stimulation of 18-hydroxycorticosterone and aldosterone secretion without changes in other aldosterone precursors suggests that dopamine modulates the activity of the glomerulosa 18-hydroxylase enzyme.

Correlated cholinomimetic-stimulated beta-endorphin and prolactin release in humans

Previous studies, both in animals and humans, have demonstrated that the intravenous or intraventricular administration of endogenous opioids and opiates produce dose dependent increases in plasma concentrations of prolactin. Notably, in humans, intravenous infusion of centrally active cholinomimetic drugs, such as physostigmine or arecoline, may produce significant increases in plasma concentrations of prolactin and beta-endorphin immunoreactivity. In three separate studies, conducted collaboratively between the National Institute of Mental Health and the University of California at San Diego, physostigmine and arecoline associated increases in plasma concentrations of beta-endorphin immunoreactivity were highly correlated with increases in plasma prolactin concentrations. These results are of interest because centrally active cholinomimetic drugs have been variously reported either to have no effect, to increase, or to inhibit anterior pituitary prolactin release. We propose that cholinergic stimulation of hypothalamic beta-endorphin may represent an interesting example of peptidergic modulation of primary neurochemical effects on hypothalamic-pituitary hormonal regulation.

The value of plasma prolactin levels in the prediction of the responsiveness of growth hormone secretion to bromocriptine and TRH in acromegaly.

The mechanism of the inhibition of growth hormone secretion in response to bromocriptine and the ability of thyrotropin releasing hormone to stimulate growth secretion in acromegaly is unknown. In the present study the relationship between the plasma prolactin concentration of untreated acromegalic patients and the reaction of growth hormone to thyrotropin releasing hormone and bromocriptine was investigated. Plasma prolactin levels were elevated in thirty-three (42%) of seventy-nine untreated acromegalic patients. Seventeen patients had mildly elevated prolactin levels, but in sixteen the plasma prolactin concentration was higher than 30 ng/ml. Bromocriptine (2.5 mg) inhibited growth hormone secretion by more than 50% in 22% of the normoprolactinaemic, in 53% of the mild hyperprolactinaemic and in 88% of the patients with a prolactin level above 30 ng/ml (P less than 0.01 v. normoprolactinaemic; P less than 0.01 v. mildly elevated prolactin levels). An increase of growth hormone secretion by more than 100% of the basal value in response to thyrotropin releasing hormone was observed in 44% of the normoprolactinaemic, in 59% of the mildly hyperprolactinaemic and in 75% of the clearly hyperprolactinaemic patients; (P less than 0.01 v. normo- and mildly hyperprolactinaemic patients). An increased plasma prolactin concentration in patients with acromegaly is accompanied in most patients by a higher sensitivity of growth hormone secretion to bromocriptine.

Effect of hypothalamic surgery on prolactin release induced by 5-hydroxytryptophan (5-HTP) in rats.

Intravenous injections of varying doses of 5-HTP (1, 3 and 5 mg/100 g body wt), a precursor of serotonin, caused a significant and dose-related increase in plasma prolactin concentrations in urethane-anesthetized rats. Increases in plasma prolactin concentrations caused by 5-HTP (1 mg/100 g body wt iv) were abolished by the concomitant administration of L-DOPA (2 mg/100 g body wt iv). Plasma prolactin levels were also significantly elevated following the injection of 5-HTP in rats with complete hypothalamic deafferentation, whereas 5-HTP had no significant effect on plasma prolactin levels in rats with extensive hypothalamic ablation. These results suggest that 5-HTP causes prolactin secretion by stimulating the serotoninergic mechanism in the hypothalamus.

The effect of certain stilboestrol analogues on plasma prolactin and testosterone in the rat.

SUMMARY Oestradiol-17β, diethylstilboestrol (DES), dl-dihydrodibutylstilboestrol (dl-DHBS) and meso-dihydrodibutylstilboestrol (meso-DHBS) were injected intramuscularly into male Sprague-Dawley rats in a daily dose of 100 μg for a period of 10 days. Oestradiol-17β and DES decreased the weight of the prostate and seminal vesicles to the same extent, whereas meso-DHBS was less effective. dl-DHBS was almost inactive. Only oestradiol-17β and DES caused a decrease in the weight of the testes. The adrenal glands increased in weight after administration of either oestradiol-17β, DES or meso-DHBS. Four hormones in the plasma were measured: testosterone, androstenedi-one, prolactin and interstitial cell-stimulating hormone (ICSH). DES decreased the plasma concentration of both ICSH and testosterone. Oestradiol-17β and meso-DHBS administration resulted in a lowering of the plasma testosterone concentration with no effect on ICSH. Oestradiol-17β, DES and meso-DHBS markedly increased plasma prolactin concentrations. dl-DHBS appeared to have little biological effect causing only very small changes in all the parameters investigated.

Prolactin release in response to milking stimulus in the cow and goat estimated by radioimmunoassay.

The effect of milking stimulus on the plasma prolactin concentration of lactating cows and goats was investigated by a radioimmunologic procedure. Plasma prolactin level in seven cows was increased abruptly 1 to 2mins. after the start of milking. On the other hand, the level of the hormone was increased shortly before the onset of milking in two cows at early lactation stage. In the goats at mid-lactation stage, milking was followed by a dramatic increase in plasma prolactin concentration within 2 mins. In all the cases, plasma prolactin level reached a peak near the end of milking. The stimuli associated with milking induced an unequivocal and rapid prolactin release from the adenohypophysis in the cow and in the goat.