Objectives: The aim of our in-vivo and in-vitro experiments was to examine the role of leptin
in control of mammalian and avian ovarian functions.
Methods: Rabbits, pigs and chicken were subjected to food restriction, leptin treatment and
their combination. Concentration of hormones in blood, as well as the release of hormones
by ovarian cells, cultured with and without leptin, protein kinase blockers or after
transfection with gene constructs for protein kinases and transcription factors, and
the accumulation of substances within these cells was analysed by RIA, EIA, SDS PAGE-Western
blotting, immunocytochemistry and TUNEL.
Results: It was observed that rabbits and pigs with high plasma leptin levels have reduced
levels of ovarian steroid hormones and fertility. Leptin injections decreased levels
of these hormones in rabbit plasma. Food restriction (50%) which decreased plasma
leptin levels had no negative effect (chicken) or stimulated (rabbit) fertility. Exogenous
leptin inhibited nuclear maturation of porcine oocytes, decreased proliferation (expression
of PCNA, cyclin B1), regulated apoptosis (expression of bax, bcl-2, ASK-1, p53, TdT)
and secretory activity (release of steroids, IGF-I, oxytocin, and prostaglandins)
by cultured follicular tissue or granulosa cells isolated from rabbit, porcine and
chicken ovaries. Blockers of protein kinases (PKA, MAPK, CDC2) and the transfection
of cells with gene constructs induced overexpression of protein kinase ASK-1 and transcription
factors STAT-1, p53 and NFkB were able to modify these leptin effects.
Conclusion: These observations suggest (1) that leptin could mediate the influence of nutrition
on female mammalian and avian reproduction, (2) that leptin could be a potent and
direct regulator of basic ovarian cell functions (proliferation, apoptosis, secretory
and generative activity), and (3) that leptin can affect ovarian cells through PKA-,
MAPK-, CDC2-, ASK-1-, STAT-1-, p53- and NFkB-dependent signalling pathways.
