Allopregnanonolone alters follicular and luteal dynamics during the estrous cycle

ASENSIO JOANA; LACONI MYRIAM; ANTONELLA R. R. CÁCERES; PELEGRINA, LAURA T; SANHUEZA MARÍA ÁNGELES

Concón

Workshop; 4th International Workshop in Neuroendocrinology; 2017

Universidad de Chile

Allopregnanolone is a neurosteroid synthesized in the central nervous system independently ofsteroidogenic glands, and it influences sexual behavior and anxiety. Experiments were designed toevaluate the effect of a single pharmacological dose of allopregnanolone on folliculogenesis, apoptosis,proliferation and angiogenesis throughout the estrous cycle. The endocrine profiles and enzymaticactivities of critical steroidogenic proteins were also determined. Allopregnanolone was injected duringproestrous morning and then the animals were sacrificed at each stage of the estrous cycle. Ovariansections were processed to determine the number and diameter of different ovarian structures. Cleavedcaspase 3, proliferating cell nuclear antigen, α-actin and von Willebrand factor expressions wereevaluated by immunohistochemistry. Luteinizing hormone, prolactin, estrogen and progesterone serumlevels were measured by radioimmunoassay. The enzymatic activities of 3β-hydroxysteroiddehydrogenase, 3α-hydroxysteroid oxidoreductase and 20α-hydroxysteroid dehydrogenase weredetermined by spectrophotometric assays. The number of developing follicles decreased, while atreticfollicles and cysts increased in treated rats. Some cysts showed characteristics of luteinized unrupturedfollicles. Apoptosis/proliferation balance increased in follicles, and this was associated to a decrease inestrogen serum levels. Prolactin and estrogen serum levels were altered at different stages of the estrouscycle on treated rats. Allopregnanolone decreased LH surge and generated cysts without affecting thecellular pattern of vaginal smears. Angiogenic markers expression increased in treated ovaries.Apoptosis/proliferation balance and 20α-hydroxysteroid dehydrogenase enzymatic activity weredecreased in corpora lutea, thus affecting the luteolysis process. Progesterone serum levels and ovarian3β-hydroxysteroid dehydrogenase were increased in treated rats. These results suggest thatallopregnanolone interferes with folliculogenesis and steroidogenesis processes, and it also promotescorpora lutea survival and progesterone synthesis. (Supported by grants from Universidad Juan AgustínMaza and Ministerio de Salud de Mendoza)