Significant Increase In Prolactin Research Articles

Suppression of Serum Immunoreactive Human Epidermal Growth Factor by Acute Increase in Prolactin in Women.

Epidermal growth factor (EGF) is known to stimulate proliferation of various mammalian cells and secretion of prolactin (PRL) from rat anterior pituitary tumor cells. The effect of an acute increase in serum PRL induced by thyrotropin releasing hormone (TRH) or metoclopramide (MCP) on the serum immunoreactive EGF concentration was examined in nine hyperprolactinemic patients and eight normoprolactinemic women. The basal level of serum EGF in normoprolactinemic subjects was 472.8 +/- 51.1 pg/ml (Mean +/- SEM), which was not significantly different from that in hyperprolactinemic patients (487.8 +/- 22.5 pg/ml). The serum EGF concentration was decreased to 40-50% of the basal level after the abrupt increase in serum PRL induced by the injection of TRH or MCP in normoprolactinemic subjects, but no significant change in serum EGF occurred in hyperprolactinemic patients after MCP injection, in spite of a significant increase in PRL. These results suggest that an acute increase of serum PRL in normoprolactinemic women, but not in hyperprolactinemic patients, suppresses serum EGF.

Preoptic injection of VIP, but not of secretin or PHI, inhibits LH and stimulates prolactin secretion in the ovariectomized rat

The microinjection of vasoactive intestinal peptide (VIP) into the medial preoptic area rapidly inhibited pulsatile luteinizing hormone (LH) secretion within 1 h in ovariectomized rats. A transient but significant increase in prolactin (PRL) secretion occurred after VIP injection coincidentally with the initiation of the inhibition of LH pulses. Preoptic microinjections of secretin or peptide histidine isoleucine amide (PHI) did not have such effects. These results suggest specific actions of VIP, despite its structural similarity to secretin and PHI, on the preoptic mechanisms governing LH and PRL secretion in ovariectomized rats.

Prolactin and stress

AbstractThere is evidence that stress influences prolactin secretion in animals and humans. Various situations and laboratory stressors can induce a significant increase in prolactin secretion.In animal studies, adaptation to the stress seems to be accompanied by a diminished response of prolactin. This habituation to chronic stress displays a pattern that seems to be stressor‐specific.In flight experiments with human subjects, a similar process of habituation in the prolactin response has been observed in pilots.Given the fact that certain individuals might not habituate to chronic psychogenic stressful stimuli, their behavioral responses to stress might lead them to different neuroendocrine responses. This might explain the individual differences observed in the impact of stress on physical and psychological well‐being.Prolactin might become an important tool in exploring the physiopathologic consequences of certain behaviour patterns and a useful neuroendrocine correlate of the individual response to what we define as stress.

Changes in serum prolactin after electroconvulsive and epileptic seizures.

Serial serum prolactin (PRL) concentrations were measured after epileptic seizures and seizures following electroconvulsive therapy (ECT). There was a large and rapid rise in PRL after ECT seizures but a much more variable PRL response after spontaneous seizures. Only epileptic seizures of longer duration and of grand mal character resulted in a more substantial rise in PRL. In ECT seizures there was a significant positive correlation between the duration of seizures and the rise in postictal PRL. The postictal PRL curves over 24 h were similar in both spontaneous seizures and ECT seizures. Interictally there were no difference in PRL levels between epileptic patients compared to patients with other neurological diseases or healthy volunteers. Chronic treatment with drugs affecting dopamine transmission had a profound effect on PRL secretion, and a dose-dependent significant increase in PRL with neuroleptics was observed.

Prolactinemia during the menstrual cycle. A possible role for prolactin in the regulation of ovarian function.

We measured the concentration of circulating prolactin (PRL) in the serum during ovulatory and anovulatory cycles of normoprolactinemic menstruating women. The results demonstrate that during the luteal phase of ovulatory cycles a significant increase of PRL is observed together with that of progesterone. On the contrary, in menstruating women with anovulatory cycles we could not detect these increases. These data, analyzed together with the concomitant changes of gonadotrophins secretion, suggest a possible luteotrophic action of PRL in humans during the menstrual cycle.

Influence of sequential doses of 5-hydroxytryptophan on prolactin release

It is known that the administration of serotonin or its precursors induces the release of prolactin. This study was performed (1) to determine the minimal dose of 5-hydroxytryptophan that would produce a consistent and significant prolactin increase and (2) to establish the frequency of 5-hydroxytryptophan administration necessary to induce a persistent prolactin increase. Nine normal male subjects participated in 27 independent studies following pretreatment with 100 mg of carbidopa given every 8 hours for 2 days. Doses of 0.2, 0.4, and 0.8 mg/kg/hr of 5-hydroxytryptophan were initially infused for 30 minutes, and serum prolactin was measured every 15 minutes for 212hours. The urinary 5-hydroxyindoleacetic acid/creatinine ratio was determined in aliquots collected during 3 hours before, during, and after the intravenous infusion. 5-Hydroxytryptophan at a dosage of 0.4 mg/kg/hr was the minimal amount to elicit a consistent and significant prolactin increase (p < 0.01). A positive correlation (r = 0.907, p < 0.002) was also demonstrated between the maximal prolactin response and the 5-hydroxyindoleacetic acid/creatinine ratio. Thus 0.4 mg/kg/hr of 5-hydroxytryptophan was administered sequentially three times at intervals of 2, 4, 6, 8, and 12 hours. With exception of the 12-hour interval a significantly smaller plasma prolactin increase was seen following the third dose of 5-hydroxytryptophan (p < 0.05). Furthermore, the nadir for this diminished prolactin response occurred at 4 hours (p < 0.01). This phenomenon may represent a down regulation of the serotonin receptors induced by the repetitive administration of 5-hydroxytryptophan. In conclusion, this study has demonstrated a dose-related prolactin response to increasing doses of 5-hydroxytryptophan. The maximum down regulation of prolactin release occurred when 5-hydroxytryptophan was administered at 4-hour intervals.

Prolactin response after gonadotropin-releasing hormone in the polycystic ovary syndrome

The administration of gonadotropin-releasing hormone (GnRH) has been shown to stimulate prolactin (PRL) release under certain conditions. The authors compared PRL responses after GnRH in normoprolactinemic patients with the polycystic ovary syndrome (PCO) with those of normal ovulatory women in the follicular phase. Seven of 15 patients had a significant increase in PRL after GnRH, whereas none of the control subjects had a positive response. After 1 week of oral L-dopa, the responders no longer exhibited this positive response. Baseline PRL levels in responding patients with PCO were similar to levels in control subjects, whereas nonresponding patients with PCO had higher PRL levels. Baseline follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratios were higher in patients with a positive response. The positive PRL response after GnRH was not correlated with baseline serum LH, the LH/FSH ratio, delta maximum LH responses, serum testosterone (T), unbound T, or baseline PRL. The positive response correlated positively with serum levels of unbound estradiol (P less than 0.05) and serum unbound estradiol/unbound T ratios (P less than 0.01). These data suggest that under certain conditions a subgroup of patients with PCO may demonstrate a positive PRL response after GnRH. Dopamine, gonadotropins, and estrogen may play a role in this interaction.

Sex steroids modulate prolactin response to naloxone in postmenopausal women.

To evaluate whether ovarian steroids modify the prolactin (PRL) response to opioid receptor blockade, the effects of naloxone infusion (1.6 mg/h for 4 h) on PRL secretion were studied in 5 postmenopausal women. Naloxone infusion was performed in basal conditions and after chronic oral treatment with conjugated estrogens (CE) (1.25 mg/day, for 20 days) or CE plus medroxyprogesterone acetate (MPA) (10 mg/day, for 20 days). Under basal conditions, 17 beta-estradiol, estrone, gonadotropin, and PRL plasma levels were in the normal range for postmenopausal women, and naloxone failed to affect PRL secretion. Naloxone induced a significant PRL increase after CE treatment alone (p less than 0.001) or in combination with MPA (p less than 0.001). The increase was significantly higher (p less than 0.05) after CE + MPA treatment than after CE treatment alone. These data suggest that steroids modulate the stimulatory effect of naloxone on PRL secretion in postmenopausal women.

Plasma prolactin changes following fenfluramine in depressed patients compared to controls: An evaluation of central serotonergic responsibility in depression

In an attempt to evaluate the responsiveness of the serotonergic neurotransmitter system in depression, fenfluramine, a serotonin releasing agent, was administered to 18 depressed patients and 10 controls, and placebo was administered to 16 of the depressed patients in a double-blind paradigm. Plasma prolactin levels were measured prior to and for five hours following fenfluramine. Fenfluramine produced a significant increase in prolactin in both patients and controls. However, the prolactin response to fenfluramine whether measured as an absolute increase or percent increase from baseline was significantly less in depressed patients than controls. This difference remained equally statistically significant when age-and-sex-matched pairs of depressed patients and controls were compared. These results suggest that the central serotonergic system is less responsive in depressed patients than controls.

Depending on the stimulus, central serotoninergic activation by fenfluramine blocks or does not alter growth hormone secretion in man.

The role of serotonin (5-HT) in the hypothalamic regulation of human growth hormone (GH) was reassessed through the use of fenfluramine, which selectively releases 5-HT from presynaptic terminals. Oral administration of L-dopa plus propranolol induced a potent and sustained GH release in the subjects tested (26 +/- 6 ng/ml). The administration of fenfluramine (20 mg i.v. as bolus plus 20 mg/30 min i.v.) completely suppressed the L-dopa-induced GH secretion (2 +/- 09.5 ng/ml). On the other hand, when arginine (30 g/30 min i.v.) was used as a GH stimulant of medium intensity (12.7 +/- 2.8 ng/ml), fenfluramine at the same dose was not able to alter the pattern of pituitary secretion (11.5 +/- 4.2 ng/ml). Fenfluramine alone induced a slight nonsignificant decrease in GH values with a parallel and significant increase in prolactin (PRL) secretion in accordance with the proposed serotoninergic activity of the drug. Rat PRL secretion by pituitaries incubated in vitro was inhibited by dopamine. Fenfluramine added to the system did not counteract the dopaminergic reduction of PRL release, making unlikely the possibility of an antagonism at the dopaminergic receptor as mechanism of action of fenfluramine on PRL secretion. In conclusion, depending on the stimulus under study, serotoninergic activation by fenfluramine either inhibits or does not alter GH secretion in man. No proof of a serotoninergic stimulatory component on GH regulation has been detected in this study. Fenfluramine is a valuable tool in neuroendocrinological studies, dealing with serotoninergic mechanisms.

Effects of handling and ether anesthesia on serum prolactin levels in the golden hamster.

The effects of handling and ether stress on serum prolactin (PRL) levels in gonadally active and gonadally regressed male golden hamsters and in females in different stages of the estrous cycle were examined. Males, regardless of reproductive state or photoperiod, showed no significant alterations in serum PRL levels following exposure to ether and cardiac puncture, in contrast to females, which showed a significant elevation in serum PRL following these two procedures. This increase was small and inconsistent in females etherized for 1 min, but it was very pronounced in females etherized for 6 min. In females there was also a slight but significant increase in PRL following transfer from the animal room to the laboratory. Thus, routine experimental manipulations, such as moving the animals to a laboratory and ether exposure, induce significant and variable elevations of serum prolactin in female hamsters.

Stimulation of prolactin secretion by neuroleptics in rats with medial basal hypothalamic lesions.

The ability of dopamine receptor antagonists to stimulate prolactin release in rats with medial basal hypothalamic lesions was investigated. Starting levels of prolactin were elevated to approximately 400 ng/ml in animals in which the tuberoinfundibular dopaminergic neurons were completely destroyed by the lesion. In lesioned animals, chlorpromazine administration at doses of 0.1 and 5 mg/kg induced a further 2- to 3-fold significant increase in plasma prolactin levels. the incubation of anterior pituitaries from lesioned animals with 10(6) M chlorpromazine had no effect on prolactin secretion, thereby eliminating the possibility that chlorpromazine itself stimulates prolactin release from the anterior pituitary. A similar increase in plasma prolactin in lesioned rats was also observed with the potent dopamine antagonist d-butaclamol (1 mg/kg). The effect was stereospecific since the inactive isomer l-butaclamol did not produce any change in the circulating levels of prolactin. Pimozide, another dopaminergic antagonist, was ineffective in inducing a further increase in prolactin in lesioned rats when 0.63 mg/kg was used. However, at a 10-fold lower concentration (0.63 mg/kg), pimozide stimulated a significant increase in prolactin in lesioned rats. The involvement of an alpha-adrenergic mechanism was ruled out by the inability of phentolamine (2.5 mg/kg) to increase prolactin secretion. These data suggest that dopaminergic antagonists can further increase prolactin levels in medial basal hypothalamus-lesioned rats possibly by blocking the inhibitory action of dopamine from nonhypothalamic sources, or by releasing a substance which possesses prolactin-releasing activity.

TSH and prolactin stimulation by the decarboxylase inhibitor benserazide in primary hypothyroidism.

200 mg of the 4-aromatic amino acid decarboxylase inhibitor benserazide were administered orally to five patients with primary hypothyroidism. Benserazide induced a significant increase in prolactin and TSH plasma concentration in all subjects. Since the drug blocks the conversion of DOPA to dopamine, these hormonal changes may be due to a reduction in circulating and/or median eminence levels of dopamine.

Effect of acute ethanol ingestion on integrated plasma prolactin levels in normal men

Healthy male subjects ingested 1.0 g ethanol/kg (Alcohol Day) and caloric equivalents of sucrose (Control Day). Plasma prolactin was determined on samples collected at 20-min intervals by serial constant blood exfusion, from 2 hr before to 4 hr after the drink. In 14 of the 15 men studied, plasma prolactin levels during the 2-hr period after alcohol administration were elevated an average of 31% above values for the preceding 2-hr period. Data pooled for all subjects revealed a small but statistically significant increase in prolactin coinciding with ascending and peak concentrations of blood alcohol. A significant increment in prolactin was associated with peak blood alcohol levels when values were compared between control and alcohol treatment days. Although of statistical significance, these transient and variable increases were within the normal range of basal prolactin levels for most subjects and are unlikely to be physiologically meaningful.

Pregnancy Induction after Bromocriptine-Cyclofenil Treatment in some Normoprolactinemic Anovulatory Women

It is known that bromocriptine treatment can restore gonadal function in normoprolactinemic anovulatory women, but its mechanism of action remains unclear. We employed bromocriptine together with cyclofenil, a commonly used ovulation inducer, to induce pregnancy in 13 normoprolactinemic infertile patients aged 20 to 37 years, all of whom had anovulatory cycles and no endocrine disorders. They had failed to conceive after many treatment trials with human chorionic gonadotropin, human menopausal gonadotropin, clomiphene, and cyclofenil. Each agent had been administered alone or in association. Before the treatment, a standard luteinizing hormone (LH)-releasing hormone (LHRH) test (100 μg intravenously) was performed for each woman to evaluate serum gonadotropin and prolactin response. The follicle-stimulating hormone and LH release after LHRH administration was normal, blunted, or clearly poor. In four women we observed an unusual and significant increase in prolactin (PRL) concentrations above the basal levels (“phasic” hyperprolactinemia). The schedule of treatment was as follows: cyclofenil (600 mg/daily) from the 5th to the 12th days of the cycle, and bromocriptine (2.5 mg/daily) from the 5th to the 26th days of the cycle. Five patients became pregnant after the first cycle of treatment; five conceived after the 2nd month; in three the treatment was stopped after three unsuccessful trials. In four cases a normal baby was delivered after a normal pregnancy; five women are pregnant at present. One patient aborted spontaneously. All four women with “phasic” hyperprolactinemia conceived after two treatment trials at the most. The mechanisms by which bromocriptine probably could have been able to restore fertility are discussed.

D-Amphetamine raises serum prolactin in man: Evaluations after chronic placebo, lithium and pimozide treatment

One of the major biochemical effects of d-amphetamine is the release and uptake inhibition of dopamine (DA). We measured the effect of d-amphetamine upon prolactin release which is inhibited by DA and stimulated by serotonin. d-Amphetamine (20 mg i.v.) significantly raised the serum prolactin levels of drug-free schizophrenic patients over preinfusion levels and levels following a paired placebo lactose infusion. Amphetamine infusions were repeated after both chronic DA blockade with pimozide and after chronic lithium treatment that has been reported to attenuate amphetamine effects. These chronic pretreatments did not prevent significant increases in prolactin following d-amphetamine infusions. Pimozide raised preinfusion prolactin levels but lithium had no effect. Further studies are needed to clarify the d-amphetamine-induced rise in prolactin.

Sex differences in prolactin release after stimulation of the preoptic-suprachiasmatic region at selected pulse frequencies in castrated rats

Long-term adult castrated rats of either sex were used. The preopticsuprachiasmatic (POA-SCH) region was stimulated bilaterally with 200-μA monophasic pulses of 0.5-ms width, in trains of 30 s on :30 s off, and at 10 or 50 Hz during 30 min under pentobarbital anesthesia. Sequential blood samples were taken starting immediately before stimulus onset and thereafter every 30 min during a 90-min period. Plasma luteinizing hormone (LH) and prolactin were measured by radioimmunoassay in the same sample. LH concentrations in control samples in both sexes were significantly reduced compared to values obtained in trunk blood after decapitation of unanesthetized rats. Stimulation at 10 Hz induced a significant rise in LH values in both sexes, with similar response profiles. Stimuli of 50 Hz delivered only in females resulted in LH values comparable to those obtained after stimuli applied at 10 Hz. Maximum average responses had values similar to those obtained in decapitated animals. In male rats, 10-Hz stimulation resulted in a significant prolactin increase. A similar stimulation in females was not effective in inducing significant prolactin changes, but stimuli delivered at 50 Hz resulted in a significant, brief increase, with a response profile different from that obtained in males. Current results indicate (a) the efficiency of “low”-frequency stimulation of the POA-SCH region to induce the release of LH and/or prolactin in castrated animals; (b) the similarity in the LH response profiles in both sexes; (c) the existence of sex differences in the prolactin release response to electrical stimulation of the POA-SCH region; and (d) the possibility of affecting differentially LH and prolactin release control mechanisms based on the temporal pattern of electrical stimuli.

Interrelationships between maternal and cord prolactin, progesterone, estradiol, 13,14-dihydro-15-keto-prostaglandin F2α, and cord cortisol at delivery with respect to initiation of parturition

Estradiol, progesterone, prolactin, and 13,14-dihydro-15-keto prostaglandin F2α (PGFM) were measured in both maternal and cord venous blood obtained at the time of delivery in 24 maternal infant pairs evenly divided among six different physiologic groups. Progesterone and prolactin were significantly higher and estradiol was significantly lower in cord than in maternal blood. There were no significant differences between the groups for cortisol, estradiol, or progesterone in maternal or cord blood. A significant increase in prolactin was demonstrated in women receiving oxytocin for induction of labor. Both estradiol and PGFM were highly correlated between maternal and cord blood. PGFM was significantly higher in cesarean section patients in labor than in those not in labor in both the maternal and cord circulations. Among those delivered vaginally, PGFM tended to be higher in those in spontaneous labor than in those with induced labor. PGFM in induced labor was intermediate between spontaneous labor patients delivered by cesarean section and those delivered vaginally. Duration of labor was negatively correlated with cord estradiol concentration. The physiologic significance of these findings is discussed.

Evidence for a Role of Prolactin in Prostate and Seminal Vesicle Growth in Immature Male Rats

To determine if prolactin secreted endogenously by anterior pituitary grafts could augment male accessory organ weights, single anterior pituitary grafts were placed under the kidney capsule of male rats, whereas control animals received a graft of muscle. Three weeks after transplantation, the animals were sacrificed by decapitation and a significant increase in plasma prolactin was observed, which was accompanied by a highly significant increase in the weights of seminal vesicles, ventral and dorsal prostates, and adrenals. To determine the importance of testicular steroids in the response, animals were castrated. The increases in prolactin, seminal vesicle and ventral and dorsal prostate weights still occurred whether or not a small dose of testosterone replacement therapy was employed. In the presence of the pituitary graft, adrenal weight usually increased in these animals as well. To rule out a requirement for adrenal steroids in the response, adrenalectomized-castrate animals were also studied, and the increases in prolactin and prostate weights still occurred although there was no significant increase in the size of the seminal vesicles. To rule out the participation of other pituitary hormones, pituitary grafts were also placed in hypophysectomized animals, and in these animals, there was also a significant increase in prolactin, accessory sex organ and testicular weights, but the adrenals did not increase in size. The grafts failed to alter gonadotropin titers in any experiment. It is concluded that single anterior pituitary grafts are capable of secreting sufficient prolactin to increase the size of the sex accessories and sometimes the testes and adrenals of the rat. Furthermore, the effects on the male sex accessory organs were demonstrable in the absence of testicular or both testicular and adrenal steroids. The data suggest that prolactin may play a physiological role in the growth of the testes, adrenals and sex accessories.

Development of dopaminergic and estrogenic control of prolactin release in the female rat.

Plasma prolactin as determined by radioimmunoassay was barely detectable in 21-day-old fetuses and on the day of birth (day 0). It had declined by days 3–6 and then rose gradually to attain adult levels at day 35. To further evaluate (he development of the prolactin control system, the ability of estrogen to elicit prolactin release was studied at various ages by injecting different doses of estradiol benzoate (Eb) SC once daily lor 2 days and measuring plasma prolactin 24 hr after the last injection. At 11 days of age, there was no significant increase in prolactin with any of the doses of Eb used (0.05–0.4 µg/100 g body wt). In 27-day-old rats, the 0.4 µg dose induced a dramatic rise in plasma prolactin and the 0.05, 0.10 and 0.2 µg dose induced much smaller but significant increases in prolactin. By 37 days, the 0.2 µg dose became highly effective and the 0.4 µg dose induced an even larger increase. The response of adult females to this dose was significantly less than that observed in 37-day-old anima...