Pulsatile Secretion Of Prolactin Research Articles

PULSATILE PROLACTIN SECRETION IN HYPOTHALAMIC-PITUITARY DISORDERS

We have studied nine children with a variety of hypothalamic pituitary disorders and delayed puberty, before and during nocturnal pulsatile GnRH therapy given subcutaneously in a dose of 2 - 4 ug every 90-120 minutes. Initial age ranged from 13.5 - 18 years. The duration of therapy was >0.5 years. Overnight serum profiles of prolactin, growth hormone and gonadotrophins were obtained by blood sampling at 15 minute intervals.In the three severely growth hormone deficient patients there were very low levels of prolactin (0-150 mIU/L), without appreciable pulsatility or sleep-related rise. In the remainder there was no clear relationship between prolactin levels and GnRH or gonadotrophin pulses. In those patients with normal growth hormone secretion, including two with isolated gonadotrophin deficiency, there was a temporal relationship between growth hormone and prolactin pulses.These results therefore seem to contrast with data from adult studies, in that pulsatile prolactin secretion was more related to growth hormone status and release than to GnRH or gonadotrophins. This may have important implications for our understanding and management of hypothalamic-pituitary disorders.

Pulsatile secretion of prolactin and oxytocin during nursing in the lactating rat.

The secretory profile of prolactin and oxytocin in response to suckling stimuli by litters was studied in unanesthetized and urethane-anesthetized lactating rats. Serum prolactin levels were determined by radioimmunoassay. Oxytocin released at milk-ejection reflex was monitored by the changes in the intramammary pressure and/or the characteristic pup's reaction associated with the milk ejection. Serum prolactin concentrations began to rise earlier than the first milk ejection in unanesthetized rats, but they were never elevated without the appearance of milk ejections in urethane-anesthetized rats. Pulsatile fluctuation in serum prolactin levels at 6-15 min intervals was observed in the nursing period when 10 pups were suckling continually. The intermittent milk-ejection reflex occurred not always but preponderantly (64-91%) when the serum prolactin levels were at the nadir of the fluctuation. Injection of an estimated dose of oxytocin released at each milk ejection (1 mU) did not change the serum prolactin levels. These results indicate that the mechanism for prolactin release may be more susceptible to the effects of anesthesia than that for oxytocin release in response to the suckling stimuli and that the release of both the hormones is pulsatile in nature and be influenced by a common biological clock during the nursing period.

Regulation of pulsatile prolactin secretion in primates.

Pulsatile prolactin (Prl) release can be unmasked in monkeys by the chronic administration of sodium pentobarbital (NaPb). We have used this model to investigate: 1) the site within the central nervous system generating PrI pulses, 2) the modulation of PrI pulses by ovarian factors, and 3) the synchronism between PrI and lutcinizing hormone (LH) pulses. Following an initial bolus of 60 to 120 mg NaPb i.v., female monkeys (Macaca mulatta and M. nemestrina) received a constant infusion at the rate of 15 mg/h for 12 h. Blood samples were drawn every 30 mm and used to quantitate Prl and LH concentrations. 1) There was no evidence of pulsatile PrI release in 4 pituitary stalksectioned monkeys. Since these monkeys are without hypothalamic input these data suggest that the site regulating pulsatile PrI release is central (hypothalamic) rather than hypophyseal. 2) Evaluating PrI pulses in intact (n=7) and castrated (n=11) female monkeys revealed that the pulse frequency was significantly greater (P<0.01) in intact monkeys [3.9 ± 0.6 (SEM) pulses/12 h] as compared to ovariectomized ones (2.3 ± 0.2 pulses/12 h). This observation indicates that ovarian factors feed back to modulate PrI pulses. 3) The frequency of Prl (2.3 ± 0.2 pulses/12 h) and LH (2.4 ± 0.2 pulses/12 h) pulses in 11 ovariectomized animals was similar and approximately two-thirds of the pulses were in synchrony. However, there were instances of PrI puises occurring without LH pulses and vice versa. The preponderance of Prl and LH pulses that are in synchrony suggests a common biological clock which generates both PrI and LH pulses. However, the periods of asynchrony suggest the existence of intermediary steps between the clock and those hypothalamic centers responsible for the secretion of these hormones.

Pulsatile secretion of prolactin in the male rat after pimozide administration is not due to pulsatile inhibition of PIF secretion

Sequential blood samples were taken every 2 min from intact male rats implanted with a permanent indwelling right atrial cannula. The relationship between pimozide dose and prolactin secreation was established by administering graded doses of pimozide (30–3000 μg/kg) as a single bolus injection through the indwelling cannula. The maximum response of prolactin secretion was achieved with 300 μg/kg pimozide. Higher doses of pimozide did not raise further the circulating prolactin concentration suggesting that the receptors for the presumed prolactin inhibiting factor (PIF) were blocked completely at this dose. Marked pulsatile fluctuations in circulating prolactin concentration were observed after administration of pimozide, at all dosages, or of another ‘specific’ dopaminergic receptor blocking agent, d-butaclamol. Since we assume that PIF receptors are completely blocked by the higher doses of pimozide, we conclude that this pulsatile secretion of prolactin cannot be due to the inhibition of PIF secretion but may be due either to the stimulation of prolactin releasing factor (PRF) secretion, or to an inherent rhythmicity in the prolactin secreting cells.