Prolactin-Releasing Action of a Low Dose of Exogenous Gonadotropin-Releasing Hormone Throughout the Human Menstrual Cycle

Abstract

Pharmacological doses of gonadotropin-releasing hormone (GnRH) are known to induce prolactin (PRL) release in different pathological states. The same effect can be observed in postmenopausal women and during the phases of menstrual cycle characterized by high estrogen levels. With the aim to evaluate whether nonpharmacological doses of GnRH are also able to induce PRL release, gonadotropin and PRL response to a low dose of GnRH (10 µg, i.v. bolus) was evaluated in 70 normal women during different phases of their menstrual cycle. A significant PRL increase was observed in 33% of subjects during the first days of the cycle (menstrual phase; days 1–3 from the beginning of menstrual bleeding; n = 6), in 24% of subjects during early follicular phase (days – 10 to -8 from LH peak; n= 17); in 38% of subjects during midfollicular phase (days – 6 to – 4 from LH peak; n = 8); in 78% of subjects during preovulatory phase (days – 2 to – 1 from LH peak; n = 9); in 67% of subjects during postovulatory phase (days + 1 to +2 from LH peak; n = 6) and in 42% of subjects during midluteal phase (days +5 to +8 from LH peak; n = 24). In brief, the increase of mean PRL levels after GnRH administration was only significant (p < 0.05) during pre- and postovulatory phases. The percentage of patients who showed a PRL response during the different phases of menstrual cycle was significantly correlated to the mean maximal net increase of LH (r = 0.927; p < 0.01) and to the mean maximal net increase of FSH (r = 0.926; p < 0.01). In conclusion, the present data show that in normal cycling women the administration of exogenous GnRH induces PRL release even at low doses. The PRL-releasing effect of GnRH is variable throughout the menstrual cycle and it is maximal during the periovulatory period. The significant correlation between PRL release and gonadotrophs responsiveness to GnRH suggests that a paracrine interaction between gonadotrophs and lactotrophs might exist also in humans.

A Confocal Microscopic Study of Gonadotropin-Releasing Hormone (GnRH) Neuron Inputs to Dopaminergic Neurons Containing Estrogen Receptor α in the Arcuate Nucleus of GnRH-Green Fluorescent Protein Transgenic Mice

“…Our results suggest that GnRH acts on TH-IR neurons and, by inhibiting DA release, stimulates PRL release from pituitary lactotropes. Indeed, besides the well-documented role of GnRH in the regulation of gonadotropin release at the level of pituitary, GnRH physiologically modulates PRL secretion: GnRH administration increased PRL release in normal cycling women [10], and from pituitary cell aggregates [11]of normal human [13]and acromegalic subjects [9]. The proposed mechanism was the release of a paracrine factor from pituitary gonadotropes.…”

“…Estrogen stimulates the secretion of PRL and inhibits the expression of TH in the ARC [26, 27]. Since the effect of GnRH on PRL release also varies throughout the menstrual cycle [13], GnRH-induced effects on the TIDA system may involve estrogen-sensitive TH-IR neurons. This effect is maximal during the periovulatory period, indicating that the relationship of GnRH axons with DA neurons depends on steroid levels.…”

“…Although GnRH is considered a highly specific releasing factor for LH and FSH, it has also been shown to induce the release of prolactin (PRL) [9, 10, 11, 12, 13]. GnRH stimulates PRL secretion in pituitary cells in the rat as well as in normal human subjects.…”

Stimulation of Prolactin Secretion from Rat Pituitary by Luteinizing Hormone-Releasing Hormone: Evidence against Mediation by Angiotensin II Acting through a (Sar¹-Ala⁸)-Angiotensin II-Sensitive Receptor

“…In the in vivo study by Steele and Myers [26] an effect of LHRH on PRL release in adult rats was only seen when estrogen-progesterone primed ovariectomized rats were used but not when adult male rats were used. In humans the PRL response to LHRH is in fluenced by the ovarian cycle [39], Experimental condi tions also determine the PRL response to LHRH [re viewed in 22], The evidence provided in previous studies [24][25][26] for a paracrine action of All in the LHRH-lactotroph con nection is not convincing. This evidence was only based on one experimental approach: the use of an All receptor blocker.…”

Bihormonal Cells Secreting Both Prolactin and Gonadotropins in Normal Rat Pituitary Cells.

“…It is also well known that GnRH stimulates PRL secretion [4,5] and that episodic secretion of LH is frequently synchronous with that of PRL [6], but the mechanisms by which GnRH exerts its effects on lactotroph function are unclear. [7,8] and stimulates PRL release by lactotrophs co-cultured with gonadotrophs, a paracrine regulation mediated by gonadotrophs may be responsible for GnRHinduced secretion by lactotrophs [9].…”