Pituitary prolactin concentrations associated with daily prolactin surges in pseudopregnant rats

During pseudopregnancy (PSP) two surges of prolactin (PRL) secretion from the pituitary are observed, the nocturnal surge at dawn and the diurnal surge in the evening. An attempt was made to clarify the correlation between changes in serum and pituitary PRL concentrations on day 5-6 of PSP. During the nocturnal surge, pituitary PRL concentration decreased significantly from 0000 hr to 0300-0600 hr. On the other hand, the high pituitary PRL concentration remained unchanged during the diurnal surge from 1200 hr to 1800 hr. These findings suggest that the nocturnal and diurnal PRL surges are regulated by separate controlling mechanisms.     

Suppression of the prolactin surges in the pseudopregnant rat by urethane anesthesia

In pseudopregnancy of the rat prolactin (PRL) is released in the form of twice daily surges (nocturnal and diurnal surges). An attempt was made to examine the effects of urethane anesthesia on PRL surges during pseudopregnancy of the rat. In a preliminary study, using the continuous blood sampling method, the nocturnal PRL surge was completely blocked when urethane (1.0g/kg BW) was administered at 0:00 hr. Urethane (1.0g/kg BW) was injected at 0:00 or 12:00 hr, and serum and pituitary PRL concentrations were measured at 6:00 or 18:00 hr, respectively, to study the effects of urethane on nocturnal or diurnal PRL surges. There were no serum PRL surges during either the nocturnal or diurnal periods following urethane injection. The experiment examining pituitary PRL concentration at 6:00 or 18:00 hr confirmed that urethane (1.0g/kg) anesthesia suppressed the release of PRL surge from the pituitary.     

Restraint stress depresses prolactin surges in pseudopregnant rats and adrenalectomy does not alter the response

Experiments were performed to determine whether restraint stress decreases the two prolactin (PRL) surges in pseudopregnant (PSP) rats in a manner similar to the stress-induced decrease of the proestrous PRL surge. Adrenal involvement as well as adaptation of the response was also investigated. Vaginal cycles were followed and animals exhibiting 2-3 normal cycles were cervically stimulated (CS) electromechanically to induce PSP. In one experiment the effect of adrenalectomy (ADX) on the nocturnal surge (NS) was investigated and was found to have no effect. In another set of experiments the effect of restraint stress was investigated. Immediately following an initial sample, the animals to be stressed had their hind legs tied together with plastic coated bell wire. Subsequent samples were taken for 3 hours. Restraint stress decreased the NS to 15% of the initial value within 30 minutes. ADX did not alter this response. Furthermore, 6-9 days of 3 hours of restraint stress did not attenuate the stress-induced decrease of the NS. Restraint stress also depressed the diurnal surge in PSP rats. These results indicate that restraint stress applied during the two PRL surges of PSP results in significant decreases in plasma PRL and that this response is not altered by ADX or by habituation to the stimulus.     

Effects of estradiol on the prolactin surges and the feedback mechanisms of gonadotropins in pseudopregnant rats

The influences of estradiol on the prolactin (PRL) surges and on the secretion of gonadotropins (LH and FSH) were investigated in the pseudopregnancy (PSP) of acutely ovariectomized rats. The four following experimental groups were prepared: 1) intact PSP as a control, 2) ovariectomy was performed on day 0 of PSP (OVX), 3) a Silastic tube containing estradiol was implanted for day 1-4 into the OVX rats (OVX-E 1-4), and 4) the Silastic tube was implanted for day 5-8 by the same manner into the OVX rats (OVX-E 5-8). In the OVX group nocturnal (N) PRL surges were observed at 0500 h on days 4, 8 and 12 examined, and increased secretions of LH and FSH were noted. In the OVX-E 1-4 group, the N PRL surge was suppressed on day 4, and the suppressed N PRL surge did not occur on day 8, after the removal of the implanted tubes. Diurnal (D) PRL surges with LH surges were observed at 1700 h on day 4 in these rats. Similarly, more remarkable results were obtained on days 8 and 12 in the OVX-E 5-8 group than in the OVX-E 1-4.(ABSTRACT TRUNCATED AT 250 WORDS)     

Loss of hypothalamic dopaminergic control of prolactin secretion in the hyperprolactinaemic rat

The possibility that chronic hyperprolactinaemia results in loss of the ability of hypothalamic dopamine activity to inhibit prolactin secretion was studied in rats. Two degrees of hyperprolactinaemia (moderate and gross) were induced in the animals following the chronic administration of two different doses of oestradiol valerate. In rats with high chronic serum prolactin concentrations (approximately 20 times normal) there was a profound increase in prolactin secretion following inhibition of brain dopamine (DA) synthesis by 3-iodo-L-tyrosine, indicating intact and highly active hypothalamic DA-inhibitory control of prolactin release. However, the degree of hypothalamic inhibition of prolactin release relative to normal controls was significantly reduced. In animals with grossly elevated chronic serum prolactin concentrations (approximately 100 times normal) a prolactin response to DA synthesis inhibition was absent despite a highly significant reduction in hypothalamic DA concentrations induced by 3-iodo-L-tyrosine. These observations show that chronic and gross hyperprolactinaemia in the rat results in loss of hypothalamic DA inhibitory control of prolactin secretion. The use of 3-iodo-L-tyrosine to block brain DA synthesis in these studies has provided significant new data relating to prolactin control in hyperprolactinaemic states and indicates that this compound could be a useful clinical tool in the study of human hyperprolactinaemia.     

Tachykinins and the control of prolactin secretion

Tachykinins are present in the pituitary gland and in brain areas involved in the control of the secretion of pituitary hormones. Tachykinins have been demonstrated to stimulate prolactin release acting directly on the anterior pituitary gland. These peptides have also been revealed to be able to act at the hypothalamic level, interacting with neurotransmitters and neuropeptides that have the potential to affect prolactin secretion. Tachykinins seem to act by stimulating or inhibiting the release of the factors that affect prolactin secretion. Among them, tachykinins have been demonstrated to stimulate oxytocin and vasopressin release, which in turn results in prolactin release. Tachykinins also potentiated the response to vasoactive intestinal peptide (VIP) and reinforced the action of glutamate, which in turn result in prolactin release. They have also been shown to interact with serotonin, a neurotransmitter involved in the control of prolactin secretion. In addition, tachykinins have been shown to inhibit GABA release, a neurotransmitter with prolactin-release inhibiting effect. This inhibition may result in an increased prolactin secretion by removal of the GABA inhibition. On the other hand, tachykinins have also been shown to stimulate dopamine release by the hypothalamus, an action that results in an inhibition of prolactin release. Dopamine is a well known inhibitor of prolactin secretion. In conclusion, although tachykinins have been shown to have a predominantly stimulatory effect on prolactin secretion, especially at the pituitary level, under some circumstances they may also exert an inhibitory influence on prolactin release, by stimulating dopamine release at the hypothalamic level.     

Dihydrotestosterone secretion in pregnant and pseudopregnant rats

The objective of this study was to determine levels of dihydrotestosterone in the peripheral circulation and the source of its secretion throughout pregnancy and pseudopregnancy. Rats were bled from the jugular vein and ovarian or uterine vein from Day 8 through Day 22 of pregnancy and from Day 8 through the end of pseudopregnancy in various types of pseudopregnant rats. Jugular vein samples alone were obtained on the day of parturition and every fourth day thereafter during the lactational period. Our results indicate that the levels of dihydrotestosterone in the peripheral circulation were high throughout pregnancy and pseudopregnancy then declined during the lactational period. The sources of dihydrotestosterone were primarily the ovary in pseudopregnant rats and the ovary plus uterus in pregnant rats.     

Effects of (-)-trans- delta 9-tetrahydrocannabinol on serum prolactin in the pseudopregnant rat

Groups of pseudopregnant rats were injected intravenously with (-)-trans- delta 9-tetrahydrocannabinol (THC) to determine its effects on serum prolactin (PRL) and the maintenance of pseudopregnancy. A single injection of 4 mg THC/kg BW at 2400 h on the first day of leukocytic vaginal smears of pseudopregnancy (D-1) delayed the ensuing nocturnal PRL surge for approximately one hour. When THC (1.0 mg/kg BW) was administered hourly from 2400 h on D-1 through 1700 h on D-2, the nocturnal surge was blocked and serum PRL levels were suppressed until 0600 h on D-2, but not thereafter. Neither treatment altered the duration of pseudopregnancy. These results indicate that the nocturnal surge secretion of PRL during early pseudopregnancy in the rat is sensitive to THC suppression, but that this suppression is not adequate to influence the duration of pseudopregnancy. The mechanism through which THC exerts this action remains unknown.     

Inhibition of nocturnal prolactin surges in the pregnant rat by incubation medium containing placental lactogen

Rats hysterectomized on Day 7 or 8 of pregnancy continued to have nocturnal prolactin surges 1 day later. Conditioned medium obtained from incubation of Day 11 placentas infused via the jugular vein completely blocked this nocturnal surge, indicating a negative feedback of placental secretions on prolactin. Infusion of an ultrafiltrate of the conditioned medium which only contained molecules with Mr above 10,000 also blocked the prolactin surge. Next, it was determined whether this feedback of placental secretions on prolactin may work by way of hypothalamic dopamine. Levels of dopamine in hypophysial stalk blood from pregnant rats on Day 12, a time when secretion of placental lactogen is high, were not different from those in rats in which placental lactogen was absent. It is concluded that termination of prolactin surges at midpregnancy may be due to feedback of placental secretions, possibly placental lactogen, on the hypothalamus and/or pituitary. However, these experiments do not support the hypothesis that this inhibition is mediated by alteration in hypothalamic dopamine secretion.     

Effect of cysteamine on suckling-induced prolactin secretion in the rat

We have examined the effects of the thiol agent cysteamine on physiological prolactin secretion in the female rat. Administration of cysteamine completely abolishes suckling-induced prolactin secretion in a dose-dependent manner. Cysteamine treatment does not alter nursing behavior of the mothers. Further, we have found that the prolactin-depleting ability of cysteamine is not altered by a prior suckling stimulus. These results indicate that cysteamine administration inhibits physiologically-induced prolactin secretion with similar potency and efficacy as previously reported for cysteamine effects on basal and pharmacologically-induced prolactin secretion. Furthermore, the effect of cysteamine is not compromised by a previous suckling stimulus, suggesting that "depletion-transformation" of pituitary prolactin stores does not protect against the effect of cysteamine.     

Extrahypothalamic distribution of CRF-like immunoreactivity in the rat brain

CRF-like immunoreactivity was measured by radioimmunoassay in the brains of normal adult rats and found to be widely distributed in extrahypothalamic areas (e.g., thalamus, amygdala, hippocampus, frontal cerbral cortex, striatum, midbrain, pons-medulla and cerebellum) at levels approximately 10% of the hypothalamus. Sephadex G-50 gel filtration reveals that CRF-like immunoreactivity in the hypothalamus coelutes with synthetic ovine CRF and is also present in the void volume. However, in the extrahypothalamic areas of the rat brain, only CRF-like immunoreactivity that coelutes with synthetic ovine CRF was detected. High performance liquid chromatography revealed equal amounts of immunoreactivity coeluting with CRF and methionine sulfoxide CRF in hypothalamic extracts.     

Somatostatin inhibits prolactin secretion in the estradiol primed male rat

Somatostatin inhibits not only growth hormone secretion, but also the secretion of several other hormones. The role of somatostatin in prolactin (PRL) secretion has not been clearly demonstrated. The present study was undertaken to examine the effects of somatostatin on rat PRL secretion in several different circumstances where the circulating PRL level is elevated: (1) the estradiol primed intact male rat, (2) normal and (3) estradiol primed rats pretreated with pimozide, (4) normal and (5) estradiol primed hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HAG rat). Blood samples (70 microL) were taken every 2 min via an indwelling atrial cannula from conscious, unrestrained animals. In the estradiol primed intact rats, a bolus injection of somatostatin (10, 100, and 1000 micrograms/kg) lowered PRL levels in a dose-dependent manner. When the PRL concentration was elevated by the administration of pimozide (3 mg/kg), a dopaminergic receptor blocking agent, somatostatin was ineffective in decreasing plasma PRL concentration but the PRL concentration was lowered by somatostatin when the rat had been primed with estradiol. Somatostatin had no effect on the normal HAG rats, but lowered the plasma PRL concentration in the estradiol primed HAG rats. Since somatostatin inhibits PRL secretion only in the estradiol primed rats, it is suggested that estradiol priming creates a new environment, presumably via new or altered receptors, which can be inhibited by somatostatin.     

Ionic mechanisms underlying TRH-induced prolactin secretion in rat lactotrophs.

Whole cell patch-clamp experiments were performed in clonal rat pituitary cells (GH3/B6 cells) to further analyze an inward-rectifying K current (IK, IR) which is suggested to be involved in the thyrotropin-releasing hormone (TRH)-induced increase in prolactin secretion from these cells. Using the class III antiarrhythmic agent E-4031 which is known as specific blocker of ether-á-go-go-related gene (ERG) K channels, the inward-rectifying K current could be isolated as the drug-sensitive current. To elucidate in molecular basis of this current, comparative experiments were performed in CHO cells which served as heterologous expression system for RERG, the rat homologue of the human ERG (HERG). It is shown that the inward-rectifying K current has properties identical to those mediated by channels encoded by RERG. In external 5 mM K+ solution, the ERG-like current IK, IR was an outward current in the physiological potential range, and this outward current could be strongly reduced by TRH. A specific block of IK, IR was able to mimick the second phase of the TRH-response which is characterized by a depolarization and/or by an increase in the frequency of Ca action potentials. These data show, that the ERG-like current in GH3/B6 cells contributes to the maintainance of the resting membrane potential and that it plays an important part in the mechanisms of the effects of TRH leading to an increase in prolactin secretion.