SAT-005 Prolactin regulates hormone production and metabolism in LbT2 pituitary gonadotrope cell line

Abstract Disclosure: G. De Robles: None. C. Garcia: None. Z. Del Mundo: None. M. Seldin: None. D. Nicholas: None. Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among premenopausal women in which the hypothalamic-pituitary-gonadal axis is disturbed. For instance, gonadotropin-releasing hormone (GnRH) is hypersecreted from the hypothalamus and causes an increased production of luteinizing hormone (LH) in gonadotropic cells from the anterior pituitary gland. Whether other factors localized in the anterior pituitary gland contribute to the dysregulation of LH secretion is an unclear topic, but prolactin (PRL), another pituitary hormone, has been associated with metabolic phenotypes among PCOS women. We confirmed through single-cell RNA sequencing on mouse pituitaries the expression of the PRL receptor gene (Prlr) in gonadotropic cells. To observe the effects of PRL on gonadotropic cells, we treated its in vitro model, the LbT2 cell line, with various concentrations of PRL under conditions of either the presence or absence of GnRH for 30 minutes. Similar to when the LbT2 cells secrete a higher level of LH following a GnRH treatment, PRL at a low concentration (4 ng/mL) induced LH secretion at an equivalent level. When LbT2 cells were treated with GnRH and increased PRL concentrations (20 and 100 ng/mL), LH levels dropped to those comparable to untreated LbT2 cells. Following a mitochondrial stress test using a Seahorse XF analyzer, we confirmed significant increases in maximal respiration following a PRL treatment (20 and 100 ng/mL) with and without the presence of GnRH. At these specific conditions, the extracellular acidification rate also significantly increased compared to untreated LbT2 cells. Our data presented the effects of PRL on the gonadotropic cell line at both hormone synthesis and metabolism, which proposed further analysis of the underlying mechanisms that may contribute to the pathophysiology of PCOS. Presentation: Saturday, July 12, 2025