Leptin regulates GH secretion in the rat by acting on GHRH and somatostatinergic functions

Leptin is a hormonal product of adipose tissue whose expression reflects th e body state of nutritional reserves. Previous experiments have demonstrate d that leptin is one of the metabolic signals capable of regulating GH secr etion. The aim of the present study was to evaluate whether CNS-mediated me chanisms underlie the GH-releasing activity of leptin. Freely moving mature male rats were injected i.c.v with leptin or isovolume tric amounts of diluent once daily for 3 days and were killed 2h after the last administration. Central injection of leptin increased pituitary GH mRN A levels by 53.2% and hypothalamic GHRH mRNA by 61.8%, and reduced somatost atin mRNA levels by 41.5%. To evaluate the direct effect of leptin on the p ituitary, it was added alone or in combination with GHRH to primary culture s of anterior pituitary cells. Addition of leptin (10(-11)-10(-7) M) did no t alter basal GH release nor the GH-releasing activity of GHRH. These resul ts demonstrate that leptin is a metabolic signal that regulates GH secretio n in the rat by acting on hypothalamic GH-regulatory hormones.