Περίληψη:
Absence of leptin secretion compromises reproductive function and
fertility in the ob/ob mouse which, when given leptin, shows a rise in
serum LH levels and becomes fertile. Recently, the long and active
isoform of the leptin receptor was detected in the ovary. indicating
that leptin may also show direct gonad-related activity. To examine
this, we studied the effect of graded doses of human leptin on estradiol
(E-2) and progesterone (P-4) concentrations in the culture media of
human granulosa-lutein cells obtained from follicular fluid of women
undergoing in vitro fertilization. We also evaluated the mRNA expression
of steroidogenic acute regulatory protein (StAR), aromatase, and
cytochrome P450 17 alpha (CYP17) in these cells at baseline and after
exposure to leptin, Estradiol levels were significantly decreased in the
media 24 hours after incubation of the cells with increasing hLeptin
concentrations (10(-11) -10(-7) mol/l). The maximal 30 % decrease in
E-2 production was caused by the 10(-9) mol/l hLeptin concentration;
however, P-4 levels in the media were not influenced by leptin, Exposure
of granulosa-lutein cells to 10-9 mol/l hLeptin did not produce any
measurable changes on StAR, aromatase, or CYP17 mRNA expression, When
hLeptin (10(-9) mol/l) was co-incubated with increasing concentrations
of hCC (1.25-10 mIU/ml), IGF-II (15-50 ng/ml) or 1-6 desaminated ICF-II
(desIGF-II; 15-60 ng/ml), it did not modify the elevation of E,
concentrations caused by each of the different stimuli, We conclude that
leptin suppresses E-2 secretion by human granulosa-lutein cells but does
not impair the stimulatory effects of hCG and IGFs on these cells.
Leptin may play a minor, but direct regulatory role on unstimulated
human ovarian steroidogenesis by interfering with either the
translational or post-translational steps of the baseline C/P17 and/or
aromatase synthesis and/or the activation of the enzymes.
Συγγραφείς:
Ghizzoni, L
Barreca, A
Mastorakos, G
Furlini, M
Vottero,
A
Ferrari, B
Chrousos, GP
Bernasconi, S
