Effects of orexins A and B on the secretory and proliferative activity of immature and regenerating rat adrenal glands

Orexins A and B are two hypothalamic peptides, involved in the central regulation of feeding, which act through two receptor subtypes, named OX1R and OX2R. OX1R is selective for orexin-A, and OX2R binds both orexins. We have investigated the effects of three subcutaneous injections of 10 nmol/kg body weight of orexins on the secretion and proliferative activity of immature (20-day-old) and regenerating rat adrenal cortex. The presence of both OX1R and OX2R mRNAs has been detected by reverse transcription-polymerase chain reaction in adult, immature and regenerating adrenals. Orexin-A increased corticosterone plasma concentration in immature rats, but not in animals with regenerating adrenals. Both orexins raised metaphase index (%o of metaphase-arrested cells) in immature rat adrenals, orexin-B being more effective than orexin-A. In contrast, both orexins equipotently lowered adrenal metaphase index at day 5 (but not day 8) of adrenal regeneration. We conclude that orexins (1) stimulate secretion and proliferative activity of immature rat adrenals, acting through OX1R and OX2R, respectively; and (2) do not affect secretion, but inhibit proliferative activity of regenerating adrenals, mainly via the activation of OX2R.