title: Effects of leptin and leptin fragments on steroid secretion of freshly dispersed rat adrenocortical cells.
abstract: The biological actions of leptin on target tissues are mediated via several isoforms of receptors (Ob-Rs), which may differently interact with native leptin and its fragments. Based on the presence in the rat adrenals of at least two Ob-R isoforms and the conflicting findings on the effect of leptin on adrenocortical secretion, we investigated the effects of the native leptin and several leptin fragments (10(-8) and 10(-6)M) on aldosterone and corticosterone secretion from freshly dispersed rat zona glomerulosa (ZG) and zona fasciculata-reticularis (ZF/R) cells. Reverse transcription (RT)-polymerase chain reaction (PCR) showed the expression of Ob-Ra and Ob-Rb mRNAs in both ZG and ZF/R cells. Native murine leptin (1-147) enhanced aldosterone and corticosterone secretion from dispersed ZG and ZF/R cells, and similar effects were elicited by murine leptin fragment 116-130, and human leptin fragments 138-167, 150-167 and [Tyr] 26-39. Human leptin fragment 93-105 was ineffective, while fragment 22-56 decreased corticosterone output without affecting aldosterone secretion. Taken together, our findings indicate that in rat adrenocortical cells leptin and leptin fragments may differently interact with Ob-Rs or interact with different Ob-R isoforms. Moreover, they suggest that (1) the direct adrenocortical secretagogue effect of leptin mainly depends on the C-terminal sequence 116-166; and (2) the N-terminal sequence is not needed for leptin to activate Ob-Rs positively coupled to steroidogenesis, but is possibly responsible for a direct inhibitory effect on glucocorticoid secretion.
authors.affiliation: Department of Histology and Embryology, Poznań School of Medicine, PL-60781 Poznań, Poland.
authors.forename: Ludwik K
authors.initials: LK
authors.lastname: Malendowicz
authors.forename: Giuliano
authors.initials: G
authors.lastname: Neri
authors.forename: Anna
authors.initials: A
authors.lastname: Markowska
authors.forename: Anna
authors.initials: A
authors.lastname: Hochol
authors.forename: Gastone G
authors.initials: GG
authors.lastname: Nussdorfer
authors.forename: Mariola
authors.initials: M
authors.lastname: Majchrzak
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism*; D005260:Female; D006801:Humans; D020738:Leptin / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015385:Zona Reticularis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: C515448:LEPR protein, human; D020738:Leptin; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D000450:Aldosterone; D003345:Corticosterone