Endogenous Prolactin Secretion Research Articles

Site of Action of Prolactin in the Suppression of Gonadotropin Secretion During Lactation in the Rat: Effect on Pituitary Responsiveness to LHRH1

The elevated levels of prolactin associated with lactation contribute significantly to the suppression of the postcastration increase in gonadotropin secretion during lactation. This study determines the effects of prolactin on pituitary responsiveness to LHRH in the rat. Blood samples were collected before administration of LHRH (100 or 500 ng) and at 15, 30, 45, and 60 mm after treatment with LHRFI. Administration of exogenous prolactin on Days 10 and 11 postpartum to females nursing two pups had no effect on basal LH or FSH secretion Day 11 or on the LH or FSH responses after LHRH administration. Whereas ovariectomy on Day 10 resulted in a significant increase in LH secretion on Day 1 1, administration of exogenous prolactin to ovariectomized lactating females significantly decreased the postcastration rise in LH without having an effect on the LH response to LHRH. The effect of endogenous prolactin secretion was studied on Day 10 postpartum in females nursing eight pups by inhibiting suckling-induced prolactin with CB-154 for 24 h before LHRH administration. The LH response after LHRH was similar in the presence or absence of elevated levels of prolactin. However, if the pups were removed for 24 h before administration of LHRH, both basal LH secretion and the response after LHRH increased to levels observed during diestrus of the estrous cycle. The effect of endogenous prolactin secretion on the postcastration rise in LH and FSH was studied on Day 8 or 17 postpartum (5 days after ovariectomy) in females nursing eight pups. The results showed that whereas suckling plus endogenous prolactin secretion almost completely blocked any postcastration rise in LH or FSH, suppression of prolactin in the presence of suckling led to a very large increase in LH and FSH. In spite of large differences in the basal rate of LH and FSH secretion, LHRH-induced LH secretion was similar in the presence or absence of prolactin. These results indicate that in intact lactating females, prolactin has no effect acutely to suppress the basal rate of gonadotropin secretion or LHRH-induced gonadotropin secretion. In ovariectomized lactating females, the elevated levels of prolactin associated with lactation suppress gonadotropin secretion but do not appear to be acting at the level of the pituitary to decrease responsiveness to LHRH, and therefore must be acting at the level of the hypothalamus.

Effects of bromocriptine administration to pregnant rabbits upon fetal lung maturation.

If endogenous prolactin secretion is important in normal development of fetal lung surfactant, the inhibition of its secretion should be associated with delayed maturation of fetal lung. We therefore studied the effect of bromoergocriptine administration to pregnant rabbits upon lecithin content of fetal lung washes. The does were treated since the 27th day of gestation with either Mesilate of 2-Bromo-alpha-ergocriptine (C32H40BrN5O5, CH3SO3H) (Bromocriptine) (Parlodel, Sandoz) (1 mg/kg/day) or solvent twice daily until delivery. The newborns were killed immediately by intraperitoneal administration of sodium pentobarbital and tracheostomized; then lung washes were performed. The extracted lipids were plated and run on heat-activated thin layers of silica gel H. Lecithin was eluted, and phosphorus determination was performed. The level of lecithin phosphorus in the lung washes of the fetuses whose mothers received Bromocriptine was X = 2.24 +/- 0.39 microgram/g dry lung weight, whereas that of fetuses of control does was X = 6.93 +/- 2.64 microgram/g dry lung weight (P less than 0.001). The mean body weight of the fetuses from treated mothers was 38.22 +/- 6.39 g whereas that of fetuses from control rabbits was 47.63 +/- 6.94 g (P less than 0.001). The mother's body weight gain from days 26 to 30 in Bromocriptine-treated rabbits was 156.11 +/- 99.4 g, whereas that of controls was 374.38 +/- 166.21 g (P less than 0.01).

Effects of Bromocriptine Administration to Pregnant Rabbits upon Fetal Lung Maturation

Summary: If endogenous prolactin secretion is important in normal development of fetal lung surfactant, the inhibition of its secretion should be associated with delayed maturation of fetal lung. We therefore studied the effect of bromoergocriptine administration to pregnant rabbits upon lecithin content of fetal lung washes. The does were treated since the 27th day of gestation with either Mesilate of 2-Bromo-α-ergocriptine (C32H40BrN5O5, CH3SO3H) (Bromocriptine) (Parlodel, Sandoz) (1 mg/kg/day) or solvent twice daily until delivery. The newborns were killed immediately by intraperitoneal administration of sodium penthobarbital and tracheostomized; then lung washes were performed. The extracted lipids were plated and run on heat-activated thin layers of silica gel H. Lecithin was eluted, and phosphorus determination was performed. The level of lecithin phosphorus in the lung washes of the fetuses whose mothers received Bromocriptine was X = 2.24 ± 0.39 μg/g dry lung weight, whereas that of fetuses of control does was X = 6.93 ± 2.64 μg/g dry lung weight (P < 0.001). The mean body weight of the fetuses from treated mothers was 38.22 ± 6.39 g whereas that of fetuses from control rabbits was 47.63 ± 6.94 g (P < 0.001). The mother's body weight gain from days 26 to 30 in Bromo-criptine-treated rabbits was 156.11 ± 99.4 g, whereas that of controls was 374.38 ± 166.21 g (P < 0.01). Speculation: Prolactin could be involved in the normal biochemical development of the lung and also be necessary for a normal weight gain of mother and fetuses during the last stage of gestation.

A chronically hypoprolactinemic rat model: administration of lergotrile mesylate by osmotic minipump.

AbstractThe feasibility of developing a hypoprolactinemic animal model by inducing prolonged suppression of endogenous prolactin (PRL) secretion by lergotrile mesylate (LM) administered via an ip implanted osmotic minipump was investigated. The response of plasma PRL to a 3-min ether challenge was examined over 7 days in animals receiving either physiological saline or LM at rates of 2.5, 5.0, and 10.0 μg/hr via osmotic minipumps. Control animals demonstrated an increased PRL response to ether, in comparison to Day 1, upon subsequent exposures. The increased response to subsequent ether exposure was prevented by LM administration at rates of 2.5 and 5.0 μg/hr. LM at a rate of 10.0 μg/hr significantly suppressed the PRL response to ether on Days 4, 6 (P 0.002) following pump implantation. In addition, spontaneous PRL levels were examined over a 24-hr period in chronically cannulated male rats receiving either saline (n = 4) or LM at a rate of 10.0 μg/hr (n = 4), on Day 7 following pump...

Prolactin in cerebrospinal fluid: A probable site of prolactin autoregulation

The purpose of this study was to examine the thesis that increasing concentrations of prolactin within the cerebrospinal fluid (CSF) increase the activity of dopaminergic terminals within the median eminence and that this increased dopaminergic activity is temporally associated with a suppression of endogenous prolactin secretion. To avoid difficulties encountered in performing catecholamine turnovers in the undisturbed rat, the measurement of tyrosine hydroxylase was validated as an index of dopaminergic activity within the median eminence. In the median eminence, but not the medial preoptic area, parallel increases in the activity of tyrosine hydroxylase and the turnover of dopamine (but not norepinephrine) occurred following hyperprolactinemia. Twenty-six hours but not 2.5 h after the subcutaneous administration of ovine prolactin, the activity of tyrosine hydroxylase was increased in the median eminence, and endogenous prolactin secretion was inhibited. During a 26 h continuous intracerebroventricular (icv) infusion (88 ng/h) of rat prolactin, there was a complete suppression of endogenous prolactin secretion. Twenty-six but not 2.5 h after the initiation of the icv infusion of prolactin, there was an increase in tyrosine hydroxylase activity in the median eminence. The results of these studies suggest that: (1) measurement of tyrosine hydroxylase activity within the median eminence is a useful index of the activity of dopaminergic terminals; (2) increasing concentrations of prolactin within the CSF suppressed prolactin secretion by the anterior pituitary; (3) this suppression of prolactin is accompanied by an increased activity of dopaminergic terminals within the median eminence; (4) those neural structures concerned with the regulation of prolactin secretion respond directly to prolactin itself; (5) the autoregulation by prolactin of its own secretion manifests a certain latency more characteristic of a tonic rather than a phasic inhibitory control; and finally, (6) dopaminergic terminals in the median eminence but not the preoptic area appear uniquely sensitive to prolactin.

The Influence of Prolactin Secretion on Human Lactation

The elevation of endogenous prolactin secretion using thyrotopin releasing hormone was associated with significant increases in mammary milk production in postpartum women. More-over, a specific effect was seen on the percent fat composition which has been shown to rise as much as 228% over pretest conditions. As in the bovine, administration of high doses of estrogen is associated with mammary breast development and the sudden removal of this stimulus if accompanied by nipple stimulation is associated with non-puerperal lactation. The inhibitory effects of estrogen on the mammary cellular response to circulating prolactin has been deduced from studies in pregnant and parturient women by measuing the TRH-induced prolactin response. These studies support a relationship between prolactin and sex steroids on the initiation and maintenance of human lactation.

Milking-induced release of endogenous prolactin in cows infused with exogenous prolactin.

SummaryExogenous prolactin (3 or 9 mg NIH–B3/hr) or saline was infused for 2.5 hr into 6 cows. The prolactin or saline infusions were repeated on alternate days for a total of 4 days. Approximately 45 min was required to achieve a stable baseline after the prolactin infusion was started. The exogenous prolactin, which increased serum prolactin approximately 5– and 8–fold above baseline endogenous concentrations, did not prevent the release of endogenous prolactin in response to milking. When the infusion was stopped serum prolactin disappeared with a 1/2 time of 23–25 min. We conclude that the inhibitory effects of exogenous prolactin previously reported on endogenous prolactin secretion must be exerted primarily on synthesis rather than release mechanisms, or the animals may require chronic exposure to high concentrations of prolactin.The able technical assistance of Mrs. Annemieke Ambrosier is gratefully acknowledged.

Human lactational and ovarian response to endogenous prolactin release.

Radioimmunoassayable prolactin rises in postpartum women during nursing and after intravenous thyrotropin-releasing hormone (TRH). Prolactin release induced by TRH can be dissociated from the postsuckling response. In addition to this, increases in endogenous prolactin secretion are followed by marked breast engorgement and milk letdown, especially after intravenous TRH. In this group of breast-feeding women, vaginal smears remained atrophic even up to 410 postpartum days. Prolactin appears to influence the production of breast milk, and the maintenance of a regular nursing pattern seems to promote the maintenance of ovarian unresponsiveness to circulating gonadotropins.