Transient hyperprolactinemia during ovulation induction with gonadotropin releasing hormone (GnRH) pulsatile administration

Seven clomiphene-resistant normoprolactinemic anovulatory patients were treated with GnRH pulsatile administration (total 15 treatment cycles). Several problems with GnRH pulse therapy were raised through 6 unsuccessful cases. In 5 cases (10/15 treatment cycles), transient hyperprolactinemia (50-100 ng/ml) appeared immediately after the initiation of the treatment and persisted for 6-10 days. Follicle maturation and ovulation was not induced in these cases. Frequent blood sampling failed to demonstrate GnRH-induced LH secretion in 3 cases. Synchronous secretion of PRL with LH was observed when serum PRL levels were low, but not in situations with elevated serum PRL levels. The lack of GnRH-induced LH secretion indicates the down-regulation of the pituitary with increased frequency of GnRH pulses due to intrinsic and exogenous GnRH. The synchrony of LH and PRL suggests the contribution of GnRH-mediated PRL releasing factor (PRF) through a paracrine system between gonadotrophs and lactotrophs. Transient hyperprolactinemia observed in the current study might be attributable to a relative increase in GnRH to a GnRH-associated peptide (GAP), a constituent of GnRH prohormone and possessing an intrinsic effect of PRL suppression, by exogenously administered GnRH, causing overwhelming superiority of GnRH-mediated PRF. Transient hyperprolactinemia and regulation of the pituitary may hamper ovulation induction with GnRH pulse therapy when applied to cases with intact hypothalamic-pituitary axis.     

Regulation of human prolactin secretion by gonadotropin-releasing hormone in vitro

The regulation of human prolactin (PRL) secretion by gonadotropin-releasing hormone (GnRH) was evaluated with human pituitary monolayer cell cultures. Synthetic GnRH stimulated PRL secretion when exposed to cells in an estrogen-depleted environment. This response was inhibited by pretreatment of the cells with 17 beta-estradiol (E2). A 10(-5) M GnRH antagonist inhibited luteinizing hormone (LH) but not PRL secretion when cells were maintained in an estrogen-depleted environment. However, the GnRH antagonist inhibited basal PRL secretion when cells were maintained in medium containing 10(-8) M E2. The 10(-5) M GnRH antagonist, when coincubated with 10(-5) M GnRH inhibited the release of PRL in an estrogen-depleted environment. However, coincubation of the 10(-5) M GnRH antagonist with 10(-5) M thyrotropin-releasing hormone (TRH) failed to inhibit PRL secretion. Incubation of 10(-8) M TRH and 10(-8) M GnRH produced a synergistic release of PRL in an estrogen-depleted environment. These observations led us to conclude that GnRH stimulates PRL secretion by direct action on human pituitary cells and that GnRH acts either via the gonadotrope or through receptors on the galactotrope other than that acted upon by TRH to release PRL.     

Effect of clomiphene citrate on prolactin and gonadotropin release during GnRH-analog treatment

The capacity of the anterior pituitary to secrete prolactin (PRL) and gonadotropins was evaluated by TRH and GnRH stimulation, followed by metoclopramide (MC) administration 1 hour later, before and after clomiphene citrate (CC) priming in 8 endometriosis patients receiving GnRH agonist analog (Buserelin) therapy for 6 months. GnRH-analog treatment lowered the maximal PRL responses to TRH and MC stimulation in the luteal phase, compared to those of 8 normally menstruating control patients. The LH response to GnRH stimulation was also diminished, indicating pituitary desensitization, while the FSH response remained unchanged. Antiestrogen administration during GnRH-analog treatment further reduced the capacity of pituitary lactotropes to secrete PRL in TRH and MC tests, and it increased the LH response but not the FSH response to GnRH stimulation. These data suggest that CC affects the mechanisms controlling PRL and gonadotropin secretions in hypoestrogenic women after prolonged GnRH agonist analog treatment by different modes of action, the action on gonadotropes being stimulatory and that on lactotropes inhibitory.     

Influence of Danazol on gonadotropin secretion and synthesis by rat pituitary cells in cultures. Comparison with gonadal steroids

Increasing concentrations of estradiol, testosterone, progesterone (1.10(-10) to 1.10(-7] and Danazol (1.10(-9) to 1.10(-6) M) have been added to male rat pituitary cells maintained in monolayer cultures for a preincubation period of three days followed by a six hour incubation with or without GnRH (1.10(-8) M). Concentrations of LH and FSH have been assessed in the culture media and in the cells at the end of the experiments allowing an estimation of the influence of these steroids on gonadotropin release and synthesis. In these experimental conditions, estradiol does not modify basal and GnRH induced FSH release and synthesis but reduces the GnRH-induced response of LH. Testosterone and progesterone stimulate synthesis of FSH but inhibit synthesis and secretion of LH in the presence of GnRH. These results have been compared with those of literature. Danazol, in the same experimental conditions, stimulates synthesis of gonadotropins and simultaneously inhibits their release induced by the presence of GnRH. We conclude that Danazol is able to act at the pituitary level as testosterone which is in good agreement with its androgenic properties.     

Effects of estradiol and some antiestrogens (clomiphene, tamoxifen, and hydroxytamoxifen) on luteinizing hormone secretion by rat pituitary cells in culture

Primary pituitary cell cultures from adult female rats were incubated for 4 or 24 h with various concentrations of estradiol (E2) or the antiestrogens (AE) tamoxifen (TMX), 4-hydroxytamoxifen (OH-TMX), and clomiphene citrate (CC). The luteinizing hormone (LH)-response of these cultures to gonadotrophin releasing hormone (GnRH) was monitored. Treatment for 4 or 24 h with high concentrations (10(-5) M) of the AE significantly decreased the GnRH-induced LH-release by the gonadotrophs. The negative E2-effect, which is observed in this model after 4 h was enhanced and the positive E2-effect, which occurs after 24 h, was completely reversed into a negative effect by these high AE-concentrations. Treatment of pituitary cells with increasing concentrations of E2 (10(-13)-10(-6) M) or AE (10(-12)-10(-5) M) for 24 h led first to a dose dependent increase of the LH-response to 5 X 10(-10) M GnRH. At higher E2- or AE-concentrations this positive effect was lost, resulting in bell shaped dose-response curves. The following maximal effective concentrations (EDmax) were found: E2 = 10(-10) M, OH-TMX = 10(-9) M, CC = 10(-7) M, TMX = 10(-6) M. Incubation of pituitary cells for 24 h with concentrations of AE near their EDmax and stimulation with increasing concentrations (10(-11)-10(-7) M) of GnRH resulted in significant increases of LH-secretion over a wide range of GnRH-concentrations. It is concluded that AE possess marked intrinsic activities on pituitary LH-secretion: at extremely high concentrations they suppress the GnRH-induced release of the gonadotrophin. At lower concentrations they increase the pituitary LH-response to GnRH in a manner which is qualitatively indistinguishable from that of E2.     

Gonadotropin-releasing hormone antagonists attenuate estrogen/progesterone-induced hyperprolactinemia in monkeys

Previous studies have documented that exogenous gonadotropin-releasing hormone (GnRH) stimulates prolactin (PRL) secretion and augments thyrotropin-releasing hormone-induced PRL release. Further, the concomitant pulsatile release of PRL and luteinizing hormone (LH) suggests that GnRH may be an important regulator of PRL release in certain physiologic states. The authors explored this possibility by evaluating the effect of a GnRH antagonist ([Ac-pClPhe1, pClPhe2, DTrp3, DAla10]-GnRH; GnRH-antagonist) on PRL secretion in monkeys with induced hyperprolactinemia. Monkeys were given estradiol (E2) benzoate 25 mg/kg intramuscularly (IM) on cycle days 1 to 28, and a 3-cm progesterone (P) silastic capsule was placed on cycle day 15 and removed on day 28. On cycle days 15 to 28, monkeys were given IM injections of 1 mg/kg GnRH-antagonist (n = 3), 2 mg/kg GnRH-antagonist (n = 3), or vehicle (n = 3). Daily blood samples were assayed for E2, P, and PRL. The degree of PRL elevation was calculated as percent increase in area under the curve for days 15 to 28 when compared with days 1 through 14 (baseline). Luteinizing hormone levels were calculated similarly. Results indicate a dose-dependent effect of GnRH-antagonist on PRL secretion, with the larger dose producing a significantly lower hyperprolactinemic response, as well as a decline in LH. Thus, GnRH-antagonist attenuates induced hyperprolactinemia in a dose similar to that which suppresses LH release. These findings suggest that GnRH is a physiologic regulator of pituitary PRL secretion. In addition, GnRH analogs may be of benefit in controlled ovarian hyperstimulation by attenuating gonadotropin-induced hyperprolactinemia, thereby reducing potential adverse effects on fertility.     

Comparison of the effects of contraceptive steroid formulations containing two doses of estrogen on pituitary function.

A pituitary stimulation test with gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) was undertaken to determine (1) whether pituitary responses to GnRH vary in individual women taking oral contraceptive steroids over time, (2) whether a less suppressive pituitary gonadotropin effect is produced by formulations containing less than 50 microgram of estrogen, and (3) to obtain more information concerning prolactin secretion in users of oral contraceptive steroids. The same subjects who had had a suppressed luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response 6 to 9 months previously also had a suppressed response, indicating that this effect persists over time. Contraceptive formulations containing less than 50 microgram of estrogen have a lesser suppressive effect on LH release than do formulations containing 50 microgram of estrogen or more. The basal prolactin (PRL) response as well as the maximal PRL response to TRH were found to be significantly greater in subjects using oral contraceptives than in the control subjects. However, no difference in PRL response was found between the subjects using low or high doses of estrogen fomulations.     

Pulsatile gonadotropin secretion and basal prolactin levels during dopamine D-1 receptor stimulation in normal women.

The effect of the specific dopamine D-1 receptor agonist Fenoldopam on pulsatile gonadotropin secretion and prolactin (PRL) secretion was investigated in normal women. The gonadotropin response to subsequent gonadotropin-releasing-hormone (GnRH) administration was also studied. Eight women received 8-hour infusions of either Fenoldopam (0.5 microgram/kg per minute) (Smith Kline and French, Harrow, United Kingdom) or placebo. After 7 hours of infusion, GnRH was given intravenously. The luteinizing hormone (LH) response to GnRH was significantly higher during Fenoldopam compared with placebo (LH; 13.1 +/- 9.0 versus 9.4 +/- 4.3 IU/L). Basal LH levels, pulse amplitude, and pulse frequency during Fenoldopam infusion were not different from placebo. Prolactin levels increased significantly during Fenoldopam (24 +/- 2 micrograms/L) compared with placebo (16 +/- 2). The results suggest that D-1 receptor stimulation does not affect pulsatile gonadotropin secretion but increases the pituitary responsiveness to GnRH. Additionally, dopamine and Fenoldopam have opposite effects on PRL secretion, the latter increasing PRL levels.     

甾体避孕药对动情前期大鼠垂体贮存与释放LH的影响

本实验利用动情前期大鼠垂体对GnRH的激发效应作为模型,观察不同类型甾体避孕药(抗孕-53,18-甲基炔诺酮)处理前后垂体贮存和释放LH的关系,抗孕-53处理组剂量为3mg、0.75mg;18-甲基炔诺酮为4mg、1mg各溶于茶油0.5ml,对照组为茶油0.5ml。大鼠经两次静脉注射GnRH,其间隔为60min。血浆LH浓度达到高峰时(150min)取出垂体,用干冰速冻,称重,匀浆。放射免疫测定血浆和垂体组织内LH含量。结果表明:LH的贮存和释放有一定关系,抗孕-53处理组血浆LH浓度升高,垂体LH含量变化不明显,18-甲基炔诺酮处理组血浆LH浓度降低,垂体LH含量升高。这现象表明不同甾体避孕药对垂体释放与贮存LH有不同的影响。     

Gonadotrophin-releasing hormone (GnRH) and GnRH agonists: mechanisms of action

The hypothalamic decapeptide gonadotrophin-releasing hormone (GnRH) binds to specific receptors on pituitary gonadotrophs. These receptors belong to the family of G protein-coupled receptors. Their activation leads to phosphoinositide breakdown with generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) and diacylglycerol. These second messengers initiate Ca(2+) release from intracellular stores and activation of protein kinase C, both of which are important for gonadotrophin secretion and synthesis. Prolonged activation of GnRH receptors by GnRH leads to desensitization and consequently to suppressed gonadotrophin secretion. This is the primary mechanism of action of agonistic GnRH analogues. By contrast, GnRH antagonists compete with GnRH for receptors on gonadotroph cell membranes, inhibit GnRH-induced signal transduction and consequently gonadotrophin secretion. These compounds are free of agonistic actions, which might be beneficial in certain clinical applications.     

The endocrinology of the menstrual cycle: the interaction of folliculogenesis and neuroendocrine mechanisms

(1) The gonadotropins are secreted in a pulsatile fashion in response to the similar pulsatile release of GnRH from neurosecretory neurons centered in the arcuate nucleus of the medial basal hypothalamus. (2) The gonadal steroids appear to exert their feedback effects both directly on the pituitary and through modulation of the pulsatile pattern of GnRH secretion. They may also influence the degree of sialylation and subsequent biologic activity of the gonadotropins. (3) GnRH release is under the control of catecholaminergic neurotransmitters. Norepinephrine appears to act as an excitatory agent, whereas dopamine inhibits GnRH secretion. (4) Dopamine also directly inhibits PRL release and may be the prolactin-inhibiting factor. (5) The endorphins are endogeneous opiate peptides and are derived from a common ACTH/ beta-lipotropin precursor. Through modulation of neurotransmitter mechanisms, the endorphins may affect both PRL and gonadotropin secretion. (6) The catecholestrogens, by virtue of their structural similarity to the neurotransmitters, may mediate the central feedback actions of the gonadal steroids.     

Gonadotropin secretion in rats bearing a prolactin-secreting pituitary tumor: effects of naloxone administration

In this study the effects of the implantation of the transplantable rat prolactin (PRL)-secreting pituitary tumor 7315a on gonadotropin secretion were investigated. Hyperprolactinemia was accompanied by suppressed plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The total PRL content of the host's pituitary gland was decreased, but the glands of tumor-bearing animals contained greatly increased amounts of LH and FSH. Chronic administration of naloxone to tumor-bearing rats for 5 days further diminished the already suppressed total PRL content of the pituitary gland, normalized the total LH content, and did not affect the FSH content. The pituitary glands from tumor-bearing rats given naloxone showed a higher ability to release LH in vitro. Hyperprolactinemia in rats is accompanied by an increased total gonadotropin content of the pituitary gland with lowered circulating gonadotropin levels. Some of the PRL-induced changes on LH synthesis and release are mediated by opioid receptors in the hypothalamus, as naloxone administration reversed some of these effects.     

Modulation of prolactin responses to gonadotropin releasing hormone by acute testosterone infusions in normal women

The administration of gonadotropin releasing hormone (GnRH) has been shown to stimulate prolactin (PRL), suggesting its role as an inducer of PRL release. This study addresses whether testosterone may modulate the release of PRL with GnRH during the early follicular phase when this stimulatory effect is not usually observed. Chromatographically pure testosterone was administered intravenously to 13 women in 2 doses (100 micrograms and 1000 micrograms) over a 6-hour period. GnRH (100 micrograms) was administered as a bolus 2 hours before and 4 hours after beginning testosterone. In addition, 3 women received testosterone twice, 3 months apart, with testolactone pretreatment on the second occasion. Serum testosterone rose in all patients and achieved maximum steady-state levels by 120 minutes. Serum estradiol (E2) was increased in subjects receiving the larger dose of testosterone but was unchanged with the lower dose and with the addition of testolactone. PRL did not increase significantly after GnRH before testosterone infusion but showed a significant increase after testosterone as well as after testosterone with testolactone. This effect did not appear to be dose-related.     

Danazol stimulates the release of follicle-stimulating hormone and inhibits the release of prolactin in vitro studies on rat pituitary cell cultures

Summary The actions of danazol on the release of gonadotropins and prolactin (PRL) were investigated by using a culture of rat anterior pituitary gland cells. The addition of danazol in the range between 10^–9M and 10^–5M elevated the levels of follicle-stimulating hormone (FSH) in a dose-dependent manner. Danazol at 10^–5M caused a 70% increase in FSH levels over the control. The intracellular contents of FSH was also increased by danazol, suggesting its stimulatory effect on both the synthesis and release of FSH. Danazol had no effect on the release of luteinizing hormone (LH). Danazol diminished the sensitivity of gonadotrophs to luteinizing hormone-releasing hormone (LHRH) in that the LHRH-induced release of both FSH and LH was suppressed. The amount of PRL released into medium was decreased by danazol in a dose-dependent way.     

The influence of weight loss on the reproductive function of the female rat: changes in the estrous cycle and hypothalamo-pituitary-ovarian function during feed restriction and subsequent refeeding period

Twelve-week-old female SD rats were restricted to an 8 g/day feed intake for 2 months followed by feeding ad libitum for 3 weeks. Feed restriction resulted in weight loss and constant diestrous. A persistent increase in the hypothalamic GnRH content was observed during the underfed period. Serum LH and PRL levels dropped throughout the period but the initial reduction in the serum FSH level was observed on the 60th day. The reductions in the pituitary content of these hormones were observed on the 30th day. The decrease in the serum and ovarian E2 levels were detected on the 14th day. Anterior pituitary showed a significant response to GnRH + TRH during the course, and the relative increases in LH, FSH and PRL were greater than those in the pretreatment rats. In the course of refeeding, the body weight returned to the control level and regular estrous cycles were reestablished on the 15th and 21st day, respectively. Elevated hypothalamic GnRH content returned to the control level on the 16th day. The changes in the pituitary-ovarian axis were prompt rebound rises in serum FSH and PRL levels and pituitary FSH content, delayed restoration of serum and pituitary LH levels and serum and ovarian E2 levels, and a marked increase in the serum and ovarian progesterone levels on the 16th day. The relative increases in FSH and PRL after GnRH + TRH injection were smaller than those in the underfed period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulsatile kisspeptin effectively stimulates gonadotropin-releasing hormone (GnRH)-producing neurons

Hypothalamic kisspeptin is integral to the hypothalamic–pituitary–gonadal axis by stimulating gonadotropin-releasing hormone (GnRH) release. GnRH is released from the hypothalamus in a pulsatile manner and determines the output of the gonadotropins. However, the effect of kisspeptin on GnRH-secreting cells remains unknown. In an experiment using static cultures of GT1-7 cells, kisspeptin did not significantly increase GnRH mRNA expression. However, when kisspeptin was administered to the cells in a pulsatile manner, GnRH mRNA expression was significantly increased. Primary cultures of fetal rat brain containing GnRH-expressing neurons responded to kisspeptin and increased GnRH mRNA expression by 1.65?±?0.27-fold in the static condition. When cells were stimulated with kisspeptin in a pulsatile manner, GnRH mRNA expression was increased by up to 2.40?±?0.21-fold. In perifused GT1-7 cells, pulsatile, but not continuous kisspeptin stimulation, effectively stimulated GnRH mRNA expression. To assess the level of stimulation of GnRH neurons by kisspeptin, the expression of c-fos was examined. In GT1-7 cells, kisspeptin stimulation in the static condition failed to increase c-fos mRNA expression. However, pulsatile kisspeptin stimulation increased c-fos mRNA by 2.31?±?0.47-fold. Similar to the phenomenon observed in GT1-7 cells, pulsatile, but not static, kisspeptin stimulation significantly increased c-fos mRNA expression in the primary cultures of fetal rat brain. These observations suggest that pulsatile kisspeptin more effectively stimulates GnRH-producing cells to increase the production of GnRH.     

Leukotrienes stimulate gonadotropin release in vitro

Monolayer cell cultures of female rat anterior pituitaries were used to investigate the effect of leukotrienes (LT) LTA4, LTB4, LTC4, LTD4, LTE4 and other lipoxygenase metabolites of arachidonic acid (5-HETE, 5-HPETE, and 15-HETE) in vitro. 3H-arachidonic acid was rapidly incorporated into pituicytes and its release was enhanced by gonadotropin releasing hormone (GnRH) in superfused pituitary cells. Leukotrienes were found to be very potent stimulators of the release of luteinizing hormone (LH) when added as pulses to superfused pituicytes. At equimolar concentrations, LTA4, LTB4, LTC4 and LTE4 were found to be more potent than the physiological stimulus GnRH. LTD4 did not affect gonadotropin secretion. Other lipoxygenase metabolites of arachidonic acid, such as 5-HETE, 5-HPETE and 15-HETE were less effective on the exocytosis of LH. These results suggest that leukotrienes are potential mediators of GnRH action on gonadotropin secretion and are possible sites of regulation of pituitary function.     

Prostaglandins have no effect on spontaneous and gonadotrophin-releasing hormone stimulated luteinizing hormone release in cultured rat pituitary cells

Primary cultures of pituitary cells from adult female rats were exposed to increasing concentrations (10(-13) to 10(-6)M) of selected prostaglandins (PGE2, PGF2 alpha, PGI2, 6-keto-PGF1 alpha, and sulproston). The release of luteinizing hormone (LH) by the pituicytes was monitored. In a second series of experiments, pituitary cells were treated with prostaglandins as described above and additionally challenged with a submaximal stimulus of gonadotrophin-releasing hormone (GnRH; 10(-9) M). The spontaneous LH-release in all prostaglandin treated cultures did not differ from the controls. When stimulated with 10(-9) M GnRH, the LH-release increased approx. six-fold in all cultures, with no difference between prostaglandin treated cells and the respective controls. Thus, the prostaglandins tested - at least at concentrations less than or equal to 10(-6) M - have neither a direct positive or negative effect on pituitary LH-release, nor do they enhance or decrease the LH-releasing effect of GnRH. These prostaglandins are probably not involved in the cellular regulation of LH-release by the pituicyte.     

GnRH-antagonists in reproductive medicine

Suppression of sex steroid production based on desensitisation and down-regulation of pituitary gonadotropin-releasing hormone (GnRH)-receptors by agonistic GnRH-analogues resulting in the blockage of gonadotropin release from the anterior pituitary gland is a well-established approach in a variety of clinical conditions. Antagonistic analogues of GnRH exert their effect by competing with endogenous GnRH for pituitary binding sites. Because of the lack of any intrinsic activity of these compounds, the characteristic initial ‘flare-up’ effect of GnRH-agonist administration is absent. A more rapid suppression of gonadotropin release from the pituitary gland can be achieved, enabling shorter treatment regimes in ovarian hyperstimulation for assisted reproduction. As yet, GnRH-antagonists have attained market approval only for the indication of premature luteinizing hormone (LH) surge prevention in controlled ovarian hyperstimulation and palliative treatment of advanced prostatic cancer. However, GnRH-antagonists may be useful in a variety of other malignant and non-malignant indications where rapid sex steroid suppression is desired, such as uterine leiomyomas, endometriosis, gynaecological cancers or benign prostatic hyperplasia. In the context of infertility treatment, available data on the application of GnRH-antagonists in the treatment of endometriosis and uterine leiomyomas are reviewed.     

The effects of insulin-like growth factor-I (IGF-I) and IGF-II on prolactin (PRL) release from human decidua and amniotic fluid circulation

It has been reported that insulin-like growth factor (IGF) may play an important role in the feto-placental environment during pregnancy. The present study was undertaken to investigate the effect of IGF-I and IGF-II on prolactin (PRL) release from human decidual cells in vitro and in vivo. The human decidua in early pregnancy was obtained by D & C, and was enzymatically dispersed into a monocellular suspension. Monolayer cultures of these cells were exposed for 96 hours to either control media or medium supplemented with IGF-I and IGF-II. PRL levels in the media were measured by EIA. Five days after dispersion, the intracellular calcium concentration [( Ca]2+i) in cultured decidual cells was measured by the Fura-2 fluorescence method with a Spectrofluorometer. PRL and IGF-I levels in amniotic fluid of 2nd trimester and term pregnancy were measured by RIA for in vivo study. In an in vitro study, IGF-I increased PRL release from decidual cells significantly during a 96 hour culture. However, IGF-II did not enhance this PRL release. IGF-I stimulation had no effect on [Ca]2+i. In an in vivo study, amniotic fluid IGF-I levels in the 2nd trimester (139.8 +/- 28.1 ng/ml) were significantly higher than those in term pregnancy (46.4 +/- 14.2 ng/ml), and a significant positive correlation (r = 0.852, p less than 0.001) was observed between IGF-I and PRL levels in the amniotic fluid. The present in vivo and in vitro studies indicated that IGF-I plays an important role in PRL release from decidua into amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS)