EFFECT OF ALLOPREGNANOLONE INTRABURSAL ADMINISTRATION, ON THE RAT UTERUS. FIRST FINDINGS

CÁCERES, ANTONELLA ROSARIO RAMONA; SANHUEZA, MARÍA DE LOS ÁNGELES; CARDONE, DANIELA ALEJANDRA; CUELLO-CARRIÓN, D.; LACONI, MYRIAM RAQUEL

San juan

Congreso; XLI Reunión Anual de la Sociedad de biología de Cuyo; 2024

Sociedad de Biología de Cuyo

Allopregnanolone (ALLO) is a neuroactive steroid, a metabolite of progesterone, and an allosteric modulator of the GABAA receptor. ALLO is produced in the ovaries at concentrations similar to progesterone and with a comparable secretion rate. Previous results showed that ALLOadministered intrabursally produces changes in ovarian morpho-physiology and steroidogenesis. The effects that these changes produce in uterine tissue are unknown, as well as whether the administration of a specific GABAA receptor antagonist, such as bicuculline (BIC), couldreverse them. The aim of this work was to evaluate the effect of an ovarian intra-bursal administration of ALLO and BIC on uterine histoarchitecture and serum estrogen and progesterone concentrations. For this, 60-day-old virgin female Sprague Dawley strain rats (250 -300g), exhibiting at least 2 – 3 regular cycles were used. The animals received an intrabursal administration of saline (control) or the treatments (ALLO 6µM and BIC 5 µM) on the day of proestrus and were sacrificed 24h later, in estrus. Serum estrogen and progesterone concentrationswere measured by CLIA and serial uterine horn sections stained with hematoxylin-eosin were analyzed. Treatment with ALLO resulted in a significant increase in serum estrogen and progesterone concentrations. ALLO induced a significative decrease of the myometrial thickness,the administration of BIC before ALLO inhibited this effect. Analysis of the endometrial luminal epithelium showed that ALLO treatment induced a significant decrease in the thickness of the epithelium, accompanied by an increase in mitoses and a decrease of epithelial degeneration and necrosis. In conclusion, the effects of ALLO at the ovarian level show consequences on uterine histoarchitecture and could be due to RGABAA modulation. This is consistent with its luteotrophic potential. ALLO produces changes in serum hormone concentrations, which may alter the reproductive axis. ALLO is a highly versatile molecule with considerable pharmacological potential on female reproductive physiology. Further studies of the effects of this molecule on the female reproductive system are needed.