Neurosteroids & Reproduction

LACONI, MYRIAM R

Con Con

Workshop; International Workshop in Neuroendocrinology; 2017

Sociedad de Neuroendocinologia

Neuroesteroids & ReproductionTounderstand the role of neuroactive steroids in physiopathology of reproduction,it is essential to review the current knowledge on this field. Research aboutthe neuroactive steroids modulation over female reproductive functions, hasgrowth during the last two decades. Knowledge of the chemical structure ofsteroids is essential for their detection and the understanding their role inphysiological and pathological conditions. We putt particular emphasis on theassays developed to assess their actions in ovarian physiopathology in rats andin human cancer cell lines. Allopregnanolone is a neuroactive steroidsynthetized in the CNS and in steroidogenic glands, and it influences ovarianmorpho-phisiology and sexual behavior. Experiments were designed to evaluatethe effect of a pharmacological dose of allopregnanolone on folliculogenesis,apoptosis, proliferation and angiogenesis. The endocrine profiles and enzymaticactivities of steroidogenic proteins were determined. Developing folliclesdecreased, atretic follicles and cysts increased in treated rats.Apoptosis/proliferation balance increased in follicles, and this was associatedto a decrease in estrogen levels. Angiogenic markers expression increased intreated ovaries. Apoptosis/proliferation balance and 20α-hydroxysteroiddehydrogenase enzymatic activity were decreased in corpora lutea, thusluteolysis was delayed. Progesterone levels and 3β-hydroxysteroid dehydrogenasewere increased in treated rats. These results suggest that allopregnanoloneinterferes with folliculogenesis and steroidogenesis processes and it alsopromotes corpora lutea survival and progesterone synthesis. Moreover,allopregnanolone was probed in ovarian cancer cell lines and here Allopregnanolonehas a dual effect, dependent on concentration and time. ALLO stimulatedproliferation, in a concentration-dependent manner at 72 h but inhibited theproliferation of tumor cells when stimulated for 4 h (p <0.001).Allopregnanolone stimulate migration and clonogenic capacity at physiologicalconcentrations. Thecurrent challenge now is to identify and quantify using appropriate methodsneuroactive steroids both  in culturemedium and in ovary and brain tissues in the context of animal and clinicalstudies to reveal how their levels change under physiological and diseasestates and then, continuing working on the potential therapeutically role ofneuroactive steroids. Finally, when considering steroids therapy, one of thedisadvantages is their poor bioavailability and short biological half-lifecaused by their rapid in vivometabolism. The recent development of synthetic steroids with betterbioavailability and efficacy might constitute novel strategies for severaldisorders.