Hypothalamic GnRH expression and pulsatility depends on a balance of prolactin receptors in the plains vizcacha, Lagostomus maximus

Abstract

In mammals, gestation is considered a physiological hyperprolactinemia status. Prolactin (PRL) is one of the modulators of gonadotropin‐releasing hormone (GnRH) neurons function. The South American plains vizcacha (Lagostomus maximus) is a unique model to study the regulation of hypothalamic GnRH neurons by direct and indirect steroid‐dependent pathways. The aim was to characterize the hypothalamic expression of endocrine markers in vizcacha during gestation as well as their response to experimental induced hyperprolactinemia. The possible involvement of PRL regulatory pathways on GnRH in the context of hypothalamic and pituitary reactivation in mid‐gestating vizcachas was discussed. Using two in vivo approaches, we determined changes in the hypothalamic expression and distribution of prolactin receptor (PRLR), tyrosine hydroxylase (TH), and dopamine type 2 receptor. A significant increment in the number of tuberoinfundibular dopaminergic (TIDA) neurons was determined in the arcuate nucleus from early to term pregnancy. On the other hand, at preoptic area, the number of both TH+PRLR+ and GnRH+PRLR+ double‐labeled neurons significantly decreased at mid‐pregnancy probably allowing the recovery of GnRH expression indicating that both types of neurons may represent the key points of PRL indirect and direct pathways modulating GnRH. Moreover, in a model of induced hyperprolactinemic vizcachas, the inhibitory effect of PRL on GnRH at both expression and delivery levels were confirmed. These results suggest the concomitant participation of both PRL regulatory pathways on GnRH modulation and pinpoint the key role of PRL on GnRH expression enabling the recovery of the hypothalamic activity during the gestation in this species.

Corticogenesis and folding process of the neopallium in the South American plains vizcacha, Lagostomus maximus

“…Adult pregnant plains vizcachas, L. maximus (RRID: NCBITaxon_10154) ( n = 46, 2.5–3.5 kg body weight), were captured and embryos ( n = 46) were used for the present study. Animals were captured at the Estación de Cría de Animales Silvestres (ECAS), Villa Elisa, Buenos Aires Province, Argentina using live capture traps located in the entrance of burrows called “vizcacheras.” According to our experience and that of other research groups with this species, captures were carried out between April and August to find pregnant females in different gestation stages (Cortasa et al., 2023; Dorfman et al., 2013; Fraunhoffer et al., 2017; Jackson et al., 1996; Leopardo et al., 2011; Núñez & Bee de Speroni, 1997; Weir, 1971). Captured animals were transferred to the Animal Facilities of Universidad Maimónides and housed in cages specially conditioned for pregnant plains vizcachas, located in a temperature‐controlled room (22 ± 2°C), with ad libitum access to food and tap water.…”

Current Insights in Prolactin Signaling and Ovulatory Function

“…Moreover, the interaction of PRL with the cell membrane of GnRH neurons is not accompanied by significant modulation of its excitability [294,295]. In addition to changes in PRLR expression under physiological and pathological conditions, the abovementioned findings indicate that PRL does not act directly on GnRH neurons; therefore, the effects of PRL on gonadotropin secretion are mediated by another population of hypothalamic neurons, including those related to kisspeptin secretion [13,296,297].…”

“…PRL in a sufficiently high concentration causes suppression of GnRH neurons that are scattered between the preoptic area (POA; marked with a dashed red line) and ARC in the shape of an "inverted Y" [82]. Due to the negligible expression of PRLR in GnRH neurons, the inhibitory effect of PRL is exerted indirectly through the participation of KNDy neurons located within the ARC [13,[294][295][296][297]. PRLR stimulation of KNDy neurons leads to inhibition of KP secretion, a family of polypeptides that stimulate GnRH secretion via the KP receptor (KISS-1R, also known as GPR54) in GnRH neurons [315][316][317].…”