Centrally admiistered Allopregnanolone inhibits apoptosis in corpus luteum of rats.

LACONI M; CAVICHIA JC; STATI A; FOSCOLO M; CABRERA RJ

CELLULAR AND MOLECULAR NEUROBIOLOGY.

Humana Press

Lugar: Washington; Año: 2008

0272-4340

Rationale: Allo i.c.v interferes in luteal regression by inhibiting apoptosis and stimulating progesterone production. Neurosteroids are steroid structure hormones with neuroactive function. Neurosteroids have genomic and non-genomic actions in CNS. Non-conjugated metabolites of progesterone such as allopregnanolone (5á-Pregnan-3á-ol-20-one- ALLO) are potent positive modulators of GABAA receptors. We report the effect of allopregnanolone, on the ovulation rate and the corpus luteum regression associated to morphological feature of apoptotic cell death in cycling rats. ALLO was injected intracerebroventriculary during proestrus. The luteinizing hormone, PRL and progesterone serum levels, the ovulation test and the histological analysis were performed in the oestrum morning. The ALLO injection significantly decreases luteinizing hormone serum level and the number of oocytes on oestrus. Progesterone and prolactin serum levels were increased after ALLO injection.  An inhibition of apoptotic figures was detected in the already formed corpora lutea belonging to the previous ovary cycle (evaluated  with optic, electronic microscopy and TUNEL assay). When the GABAA antagonist, bicuculine, was injected alone or together with allopregnanolone any effect on the ovulation rate occurred and  the apoptotic cell number were recovered, then this action was blocked by bicuculine (previously we shown the same profile when LH was analized). In summary, the results of this study have stablished that the centrally administered ALLO affect the luteal regression though inhibition of apoptosis, and stimulation of progesterone production. This effect could be correlated with a previously demonstrated decrease in the DA turnover with the consequent PRL elevation rescuing rat corpus luteum. The physiological significance of these findings is that ALLO promoting corpus luteum survival by multiple pro-survival signaling pathways comprising an integrate system of non genomic and genomic mechanisms.  Then, ALLO is acting in one of the most important and closely regulated events in mammalian reproduction, the maintenance of corpus luteum.