Effect of leptin on ACTH-stimulated secretion of cortisol in rhesus macaques and on human adrenal carcinoma cells.
OBJECTIVE
Because glucocorticoids stimulate leptin release and, at least in vitro, leptin inhibits cortisol secretion, a feedback system between glucocorticoids and leptin has been proposed. However, in humans and non-human primates there are no in vivo studies to support any role for leptin in the control of the hypothalamic-pituitary-adrenal axis. In this study, we investigated the effect of leptin on (i) ACTH-stimulated secretion of cortisol in six male rhesus monkeys and (ii) basal and forskolin (FSK)-stimulated cortisol secretion by the human adrenal carcinoma cell H295R in vitro.


METHODS
In vivo studies: after suppression of endogenous ACTH with either dexamethasone (n=6) or a corticotropin-releasing factor (CRF) antagonist (d-Phe CRF(12-41)) (n=3), 1 microg bolus of human ACTH(1-24) was administered to stimulate adrenal cortisol release. Blood samples were collected every 15 min for 3 h. Leptin (1 mg) was infused over 4 h, starting 1 h before ACTH bolus.


METHODS
NCI-H295R cells were incubated for 6, 12, 24 and 48 h in the absence or presence of 20 micromol/l FSK in combination with leptin (100 ng/ml medium). Cortisol levels in serum and medium were measured by solid phase radioimmunoassay.


RESULTS
Acute leptin infusion to rhesus monkeys did not change basal cortisol levels, peak cortisol levels after ACTH(1-24) or the area under the curve when compared with studies in which leptin was not given. FSK increased cortisol levels in medium at 24 and 48 h, but leptin did not change cortisol release in either control or FSK-stimulated cells.


CONCLUSIONS
Short-term leptin infusion affected neither the cortisol response to ACTH in non-human primates in vivo nor cortisol release (basal or FSK stimulated) by H295R cells, in vitro. These data suggest that leptin may not be an acute regulator of primate adrenal cortisol secretion.
Lado-Abeal
J
J
Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Mrotek
J J
JJ
Stocco
D M
DM
Norman
R L
RL
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003366:Cosyntropin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D020738:Leptin / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008820:Mice, Obese; D011863:Radioimmunoassay; D014407:Tumor Cells, Cultured
D020738:Leptin; D003366:Cosyntropin; D005576:Colforsin; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone