Hypothalamic Prolactin Regulation of Luteinizing Hormone Secretion in the Female Rat

Abstract

Prolactin (PRL) levels increase in response to long-term antipsychotic treatment that disrupts reproductive function. Recent evidence suggests that activation of central PRL receptors (PRLR) inhibits LH secretion and in ovariectomized rats. However, the mechanisms involved, the mode of LH secretion affected and relevance to hyperprolactinemia remain unknown. We therefore investigated the contribution of central PRL/PRLR signaling to the control of estradiol-induced surges of LH and PRL and pulsatile LH secretion under basal and hyperprolactinemic conditions. First, by subjecting ovariectomized estradiol-primed rats intracerebroventricularly administered with PRL to frequent blood sampling, we demonstrated that acute activation of hypothalamic PRLR disrupts pulsatile LH secretion. Pretreatment (intracerebroventricularly) with the pure PRLR antagonist, Δ1-9-G129R-hPRL, or the γ-aminobutyric acid receptor type A antagonist, bicuculline, blocked this effect. Next, we revealed that sustained blockade of hypothalamic PRLR using Δ1-9-G129R-hPRL augmented the magnitude of LH surges induced by estradiol benzoate and progesterone treatment and suppressed the concomitant surges of PRL. Finally, we determined that acute antagonism of central PRLR is insufficient to normalize the duration of the LH pulse interval prolonged as a result of hyperprolactinemia induced by chronic exposure to the atypical antipsychotic sulpiride. These data serve as the first evidence to suggest that PRL signaling through hypothalamic PRLR inhibits pulsatile secretion of LH in a γ-aminobutyric acid receptor type A-dependent fashion and tonically restrains the magnitude of the LH surge. Furthermore, our results indicate that transient blockade of hypothalamic PRL/PRLR signaling is not an effective strategy for restoring LH pulsatility perturbed by chronic hyperprolactinemia.

Effect of steroid-free follicular fluid antiserum on reproductive endocrine profile at estrous and metestrus phases in female rats

“…They also reported activation of central prolactin receptor which suppresses LH surge through GABA/GABAAR signaling. These observations could explain the previous reports on the role of prolactin in modulating hypothalamic role in regulating mammalian reproduction (34).…”

Hypothalamic Effects of Tamoxifen on Oestrogen Regulation of Luteinising Hormone and Prolactin Secretion in Female Rats

“…Female mice with deletions of PRL receptors are infertile because of failure in luteal function and embryo implantation . On the other hand, hyperprolactinaemia is a prevalent cause of infertility in both males and females . PRL secretion is tonically inhibited by dopamine released in the ME, mainly produced by the tuberoinfundibular dopaminergic (TIDA) neurones located in the ARC .…”

Effect of GABA-T on Reproductive Function in Female Rats

“…Our study showed that GABA-T was mainly distributed in the adenohypophysis and Abat mRNA expression gradually decreased from infancy to 28 d, increased during the puberty stage, and decreased again in adulthood. Previous studies have shown that GABA can inhibit the secretion of LH and PRL through the dopamine system and the addition of GABA-T inhibitors in vitro and in vivo results in a decrease in PRL release from the pituitary [15,19,48,49]. PRL regulates the reproductive axis by acting on hypothalamic neurons expressing the Kiss1 gene [50,51], indicating that GABA-T regulates the release of pituitary hormones (LH and PRL) via the GABAergic system, thus affecting the reproductive axis.…”

“…GABA functions keep the brain strong, and it has anti-anxiety, analgesic, hypnotic and forgetting effects [13,14]. Recent studies have shown that GABA inhibits the secration of luteinizing hormone (LH) and prolactin (PRL) in the anterior pituitary gland [15], and GABA has been found in more than 30 peripheral tissues, including ovarian and fallopian tubes [16]. Other studies have shown that GABA receptors (GABAA and GABAB) can stop the sperm acrosome reaction [17] and GABA regulates follicular development and pregnancy [16].…”