Significant Increase In Prolactin Release Research Articles

Control of Prolactin Secretion by Excitatory Amino Acids

This article provides an overview of the increasing number of observations indicating that excitatory amino acids are involved in the control of prolactin secretion. The information available suggests that these amino acids exert a stimulatory action on hypophysial prolactin. Administration of a glutamate receptor agonist induces significant increase in prolactin release in rats, monkeys, and rams. In contrast, noncompetitive antagonists of N-methyl-D-aspartate receptors decrease plasma levels and attenuate the preovulatory surge of prolactin. It appears that the endogenous glutamatergic system participates not only in the regulation of basal secretion of prolactin, but also in the control of physiological prolactin responses induced by the suckling stimulus or by stress. Recent findings suggest that the glutamatergic innervation of the hypothalamic paraventricular nucleus is involved in the mediation of the neural signal of the suckling stimulus-induced prolactin release as well as in the mediation of the stress-induced release of prolactin.

Effects of changes in environmental calcium on prolactin secretion in Japanese eel, Anguilla japonica

Effects of changes in environmental Ca2+ on the secretion of prolactin, a possible hypercalcemic hormone, were examined both in vivo and in vitro in the Japanese ecl, Anguilla japonica. Transfer of seawater- or freshwater-adapted fish to fresh water, fresh water containing 10 mmol Ca2+ · 1-1 sea water, Ca2+-free sea water, or deionized water was accompanied by significant changes in plasma Ca2+ levels after 7 days, except for the fish transferred from fresh water to fresh water and from sea water to sea water. Changes in external Ca2+ concentrations did not affect plasma prolactin levels, although plasma prolactin levels as well as pituitary prolactin contents were significantly greater in fish in a hypotonic environment than those in a hypertonic environment, regardless of the external Ca2+ concentration. Hypercalcemia, induced by removal of the corpuscles of Stannius, did not alter plasma prolactin levles. Incubation of the pituitary in the medium with different Ca2+ concentrations (up to 2.9 mmol·l-1) did not affect the basal release of prolactin, except at an extremely low Ca2+ concentration (less than 0.1 mmol·l-1) where prolactin release was inhibited. Addition of Ca2+ ionophore (A23187) to the medium led to a marked and significant increase in prolactin release, indicating that an increase in intracellular Ca2+ stimulates prolactin release. However, the effect was not specific to prolactin cells; a similar increase was seen in growth hormone release. These results indicate that changes in environmental Ca2+ concentration may not be the primary factor influencing prolactin secretion in the eel; changes in environmental osmolality or Na+ levels seem to be more critical for the regulation of prolactin secretion.

Cadmium exposure inhibits the prolactin secretory response to thyrotrophin releasing hormone (TRH) in vitro

In vitro dose response (0.1–100 μM) and time course studies were performed on anterior pituitary cells isolated from female Sprague-Dawley rats in the diestrous stage of the estrous cycle. All doses of TRH produced a significant increase in prolactin release by 5 min which was sustained for 30 min. Pretreatment with 25 or 50 μM Cd for 2 or 4 h produced a significant decrease in prolactin secretion during Cd exposure and in the prolactin secretory response to 1 μM TRH. These results suggest that Cd pretreatment alters the subsequent ability of the lactotrophs to respond to the physiological secretagogue TRH. This alteration does not appear to be due to a rebound phenomenon since basal prolactin release was the same in Cd-pretreated and control cells once the metal was removed. These results suggest that Cd pretreatment produces a significant decrease in prolactin release from the anterior pituitary lactotrophs in response to subsequent TRH stimulation in vitro.

GROWTH HORMONE‐RELEASING FACTOR INCREASES SERUM PROLACTIN CONCENTRATIONS IN NORMAL SUBJECTS AND IN PATIENTS WITH PITUITARY ADENOMAS

We have examined the serum growth hormone (GH) and prolactin (PRL) response to growth hormone releasing factor (hGRF-(1-44)NH2 (GRF) 1 microgram/kg i.v. bolus) in 16 acromegalic patients (eight of whom were hyperprolactinaemic), 13 patients with microprolactinoma, and 14 healthy subjects. The GH responses to TRH and to the somatostatin analogue SMS 201-995 were also studied in acromegalic patients. In these, and in patients with microprolactinoma, GH responses after GRF (P less than 0.001 vs saline) were variable. The absolute GH increase (calculated as area under the curve) in acromegalic patients (2489 +/- 920 micrograms/l min), or in patients with microprolactinoma (1322 +/- 279 micrograms/l min) was not different from that in controls (2238 +/- 633 micrograms/l min). In addition, a significant increase in PRL release was observed after GRF in comparison to saline in acromegalic patients (P less than 0.01), in patients with microprolactinoma and in normal subjects (P less than 0.001). The PRL increase was significantly correlated with basal PRL levels in acromegalic patients (r = 0.99, P less than 0.001) and in patients with microprolactinomas (r = 0.61, P less than 0.05). Furthermore, a significant correlation was found between GH rise after GRF and basal GH, and between GH rise after GRF and GH decrement after SMS in patients with acromegaly. These results suggest that GRF can stimulate PRL release by actions on the normal pituitary and on pituitary adenomas, including microprolactinomas. Moreover, the data suggest that in acromegaly there is a relative functional deficiency of hypothalamic somatostatin.

Transient removal of dopamine potentiates the stimulation of prolactin release by TRH but not VIP: stimulation via Ca2+/protein kinase C pathway.

The effectiveness of thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) to release prolactin (PRL) after a brief interruption of the tonic inhibitory action of dopamine (DA) was investigated in enzymatically dispersed anterior pituitary cells in superfusion. We also studied the involvement of cAMP and Ca2+/protein kinase C second messenger systems in the mediation of the stimulated PRL release. Anterior pituitary cells from lactating or E2-treated rats were superfused for 10 min with secretagogues either during continual dopamine administration or 10-20 min after a 10-min transient interruption of DA (500 nM). Removal of DA for 10 min resulted in a significant increase in PRL release which had returned to basal levels 10 min after the return of DA to the superfusion. During continuous DA exposure, TRH administration (10 nM) did not alter the rate of PRL release from cells from lactating rats; however, TRH caused a 2-fold increase after the transient interruption of DA. The transient escape from DA inhibition also increased the effectiveness of TRH (100 nM) to release PRL from cells from E2-treated rats (from a 4- to a 15-fold stimulation). In contrast, VIP (0.5 or 5 microM) caused a 2-fold stimulation of PRL release in both cells treated with continuous or transiently interrupted DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Pentagastrin promotes prolactin release in patients with medullary carcinoma of the thyroid

Both calcitonin and gastrin have been found in the mammalian central nervous system, including the pituitary. Following a pentagastrin infusion in several patients with medullary carcinoma of the thyroid, we noted a coincident increase in plasma calcitonin and prolactin (PRL) levels. In order to evaluate further the influence of pentagastrin on human PRL release, a pentagastrin infusion was administered to 13 patients with active medullary carcinoma of the thyroid (MTC), eight subjects with inactive MTC, eight family members without MTC, and ten normal subjects. Plasma mean ± SE PRL levels were significantly ( P < 0.01) increased in the active MTC patients from 7.6 ± 0.5 to 12 ± 1.4 ng/ml by 15 minutes post pentagastrin. Plasma mean ± SE calcitonin levels increased in parallel with the plasma PRL levels from 0.28 ± 0.1 to a peak of 1.9 ± 0.9 ng/mL at 5 minutes post pentagastrin. A significant ( P < 0.05) correlation was found between the percentage increase in plasma calcitonin concentrations and plasma PRL levels at five and ten minutes post pentagastrin stimulation in this group of active MTC patients. Significant increases in serum calcitonin levels in the other groups post pentagastrin were of lesser magnitude and were not associated with a significant increase in PRL release. This latter observation suggested that neither the stress of the infusion nor the multiple endocrine neoplasia type 2 nor the pentagastrin was responsible for the observed increase in plasma PRL levels in the active MTC patients. These findings suggest, but do not prove, that calcitonin is a PRL-releasing factor in humans.

A study on the prolactin releasing mechanism using an in vitro perfusion system with a cell column of cultured rat anterior pituitary cells

It is well-known that the hypothalamus predominantly exerts an inhibitory control on prolactin secretion and that dopamine (DA) is the main prolactin inhibiting factor (PIF). In addition, the hypothalamus contains prolactin-releasing factors (PRF). Thyrotropin-releasing hormone (TRH), vasoactive intestinal polypeptide (VIP) and peptide-histidine-isoleucine (PHI) are the components of PRF. However, the detailed mechanism by which the peptides release prolactin (PRL) at the pituitary level is still unknown. Therefore, in this paper, an in vitro perifusion system using the cell column of cultured rat pituitary cells attached on Cytodex beads was employed to investigate the mechanism of PRL release. The rat anterior pituitary cells were isolated using collagenase, and the dispersed pituitary cells were cultured with swollen Cytodex beads in Dulbecco's modified Eagle medium (DMEM) containing fetal calf serum at 37 degrees C in 5% CO2 and 95% air for 2--3 days. The cultured anterior pituitary cells attached on Cytodex beads were packed in a column and perifused with DMEM at a constant flow rate of 0.4 ml/min using a peristaltic pump. The following results were obtained. A five minute perifusion with 100 pg/ml to 100 ng/ml TRH caused a significant increase of PRL in a dose-related manner. A continuous perifusion with 2 ng/ml or 10 ng/ml DA inhibited PRL release in a dose-related manner. When TRH at a dose of 1 ng/ml, 10 ng/ml or 100 ng/ml was perifused for 120 min at a rate of 0.4 ml/min, a large amount of PRL was released during the early period of the TRH infusion, and then the PRL release gradually decreased to the basal levels in spite of the continuous TRH infusion. An additional TRH, of which the concentration was ten-fold higher than the TRH level in the continuous infusion, when added at the end of the continuous TRH infusion, had no effect on PRL release. On the other hand, a 5 minute TRH infusion given at 30 min after the end of the continuous TRH infusion caused a significant increase in PRL release. A continuous perifusion with 1 mM 8-bromo-cyclic AMP caused a small but continuous PRL release. An additional continuous 8-bromo-cyclic AMP infusion during the late period of a continuous TRH infusion caused a continuous PRL release similar to that induced by the continuous infusion of cyclic AMP only. A short period perifusion with 1 X 10(-9)M to 1 X 10(-7)M of vasoactive intestinal polypeptide (VIP) enhanced a significant increase of PRL release in a dose-related manner, but the amounts of PRL release induced by VIP were smaller than those induced by TRH.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of serotoninergic neurones in the control of gonadotrophin and prolactin secretion in the rat.

The role of brain serotonin (5-hydroxytryptamine, 5-HT) in the control of LH, FSH and prolactin secretion was studied in two groups of experimental animals: intact adult male rats and ovariectomized adult female rats. 5-Hydroxytryptophan (5-HTP), a precursor of serotonin synthesis, and fluoxetine, a specific inhibitor of 5-HT uptake, were given either alone or together. 5-Hydroxytryptophan (50 mg/kg) was administered intraperitoneally and fluoxetine (20 μg/rat) was given into one of the lateral ventricles of the brain. Neither 5-HTP nor fluoxetine given alone affected LH secretion but combined treatment with the two drugs elicited a significant increase in serum LH levels in both intact male and ovariectomized female rats. Fluoxetine and 5-HTP, alone or together, did not modify FSH secretion in either kind of animal. In intact males and in ovariectomized females, 5-HTP induced a significant increase in prolactin release; fluoxetine alone was ineffective. In male animals treated with fluoxetine plus 5-HTP, serum prolactin levels increased but such an increase was lower than that found in the animals treated only with 5-HTP. In ovariectomized rats, the combined treatment induced an increase in serum prolactin levels similar to that found in animals treated with 5-HTP alone. These data suggested that brain serotonin exerts a stimulating effect on LH secretion in both intact male and ovariectomized rats, but that it does not play any role in the control of FSH release in either kind of animal and that central serotoninergic pathways participate in the stimulating control of prolactin release from the anterior pituitary gland. However, some of the data also suggested the possibility of the existence in the brain of serotoninergic systems inhibiting prolactin secretion.

Effects of large doses of estrogen on prolactin and growth hormone release

The effects of large doses of estrogen on prolactin (PRL) release were assessed. Circulating PRL levels in response to intravenous infusion of 17 β-estradiol (E2), at a rate of 50 μg per hour for 4 hours, were studied in 10 subjects, and a chronic administration of ethinyl estradiol (EE) at a dose of 400 μg per day, for 1 week, was evaluated in five hypogonadal subjects. There was a significant depression of serum level of PRL during the E2 infusion and a significant increase in PRL release after discontinuation of the infusion. The chronic treatment of large doses of EE induced a more rapid (within 36 hours) and a significantly greater elevation of PRL levels at the end of 1 week treatment than those found during smaller doses of EE administration, as reported previously. These data suggest that acute treatment of estrogen may have a biphasic action on the pituitary PRL secretion and that the augmentatory effect of estrogen on PRL secretion is dose-dependent in human beings.

Steroid modulation of the hypothalamic-pituitary system in the secretion of reproductive hormones

The results of a study of the inhibition and amplification of pituitary responses to the synthetic hypothalamic hormones LRF and TRF during estrogen and progesterone experiments in normal and hypogonadal women are reported. Serum luteinizing hormone (LH) follicle stimulating hormone (FSH) prolactin (PRL) and estradiol (E2) and progesterone were measured by radioimmunoassay. In 10 hypogonadal subjects there was a significant decrease in PRL levels during infusion of pharmacological doses of E2 followed by a significant increase in PRL release lasting several hours. Small doses of ethinyl estradiol (EE) induced a significant elevation of serum PRL levels with 1 week of treatment and a continued rise within 3-4 weeks to more than 3 times the initial concentration. The LH and FSH levels fell progressively to premenopausal levels at Week 4. With large doses of EE a more rapid increase of PRL levels was found and a higher elevation. Data indicate that pituitary sensitivity and reserve are modulated by estrogen and progesterone. The sensitivity appeared to be blunted. Results of experiments indicate that the pituitary gland represents a major feedback site for the regulation of optimal delivery of tropic hormones of reproduction via steroid signals. Estrogen provides a time and dose-related positive feedback loop in the augmentation of pituitary PRL secretion. Progesterone in low concentration has a facilitatory action on the pituitary response to LRF depending on prior exposure to estrogen in optimal amount and duration. Progesterone in high concentration in the midluteal phase lessens the estrogen-augmented pituitary response to LRF.

Effect of ergocornine on perphenazine-and oestrogen-induced prolactin release.

SUMMARY Both oestradiol and perphenazine induced a significant increase in prolactin release by ovariectomized rats. Ergocornine completely inhibited the initial perphenazine-induced prolactin release which normally reaches a maximum during the first 2·5 h. However, ergocornine did not prevent a significant increase in prolactin release after daily administration of perphenazine. It inhibited oestrogen-induced prolactin release. The results support earlier suggestions that prolactin release is controlled by two mechanisms. Only one of the mechanisms can be blocked by ergocornine.

STIMULATION OF PIGEON PITUITARY PROLACTIN RELEASE BY PIGEON HYPOTHALAMIC EXTRACT IN VITRO.

Previous studies from this laboratory suggested that the mechanism for control of prolactin release by the avian pituitary was different from that present in mammals. The effects of pigeon hypothalamic extracts on release of prolactin by the pigeon pituitary were determined when incubated together at 37 C for 2 or 4 hr. The effects of rat or pigeon hypothalamic extracts on release of prolactin by the pituitary of the other species were also tested. Extract equivalent to 1 hypothalamus from a parent pigeon, sacrificed on the day young were hatched, increased prolactin release 2- to 4-fold from each pituitary of 4- to 6-week-old pigeons during a 4-hr incubation period. Slight stimulatory activity was also found in hypothalamic extracts from 4- to 6-week-old pigeons, but at the dose level tested (2 hypothalami/pituitary) they did not elicit a statistically significant increase in prolactin release. Hypothalamic extracts from rats or pigeons had no effect on release of prolactin by the pituitaries of the othe...