Context:Growing evidence indicates that ghrelin may participate in the regulation of different aspects of reproductive function. The genes encoding for this peptide and its receptor are expressed in the human ovary, but their functional role is still unknown. Objective:The aim of our study was to assess whether ghrelin has any effect on steroid synthesis by human granulosa-lutein cells and to identify the receptor isoform through which this potential effect is exerted.Design, Patients, and Methods: Thirty-five women with spontaneous ovulatory cycles undergoing in vitro fertilization for infertility due to uni-or bilateral tubal impatency or male factor were studied. Granulosa-lutein cells obtained from follicular fluid were incubated with increasing amounts of human acylated ghrelin (10 Ϫ11 to 10 Ϫ7 mol/liter) either alone or together with a 1:500 concentration of a specific anti-ghrelin receptor antibody [GH secretagogue receptor 1a (GHS-R1a)]. Culture media were tested for estradiol (E 2 ) and progesterone (P 4 ). The expression of GHS-R1a and GHS-R1b in human granulosa-lutein cells was also studied by real-time quantitative PCR.Results: E 2 and P 4 concentrations in the culture media were significantly reduced by ghrelin in a dose-dependent fashion. The maximal decrease in E 2 (25%) and P 4 (20%) media concentrations was obtained with the 10 Ϫ7 and 10 Ϫ8 mol/liter ghrelin concentrations, respectively. The inhibitory effect of all ghrelin concentrations used was antagonized by the specific anti-ghrelin receptor-1a antibody added to the culture media and not by the specific anti-ghrelin receptor-1b antibody. Both 1a and 1b isoforms of the GHS-R were expressed in human granulosa-lutein cells, with the latter exceeding the former's expression (GHS-R1b/GHS-R1a ratio, 143.23 Ϯ 28.15). Conclusions:Ghrelin exerts an inhibitory effect on granulosa-lutein cells steroidogenesis by acting through its functional GHS-R1a. This suggests that ghrelin may serve an autocrine-paracrine role in the control of gonadal function and be part of a network of molecular signals responsible for the coordinated control of energy homeostasis and reproduction.

Congenital adrenal hyperplasia is a group of monogenic autosomal recessive disorders due to an enzyme deficiency in steroid biosynthesis. The most frequent form of congenital adrenal hyperplasia is 21-hydroxylase (21-OH) deficiency, which in its severe form can cause ambiguous genitalia in the female patient. Recent advances in molecular genetic analysis allow for prenatal diagnosis and treatment of at-risk fetuses. The objective of prenatal diagnosis and treatment of 21-OH deficiency is the prevention of prenatal virilization in affected female infants, reducing the risks of sex misassignment and gender confusion, and the need for corrective genital surgery. Prenatal treatment of 21-OH deficiency is effective in reducing genital ambiguity, and short-term outcome studies of children exposed to dexamethasone in utero indicate no significant adverse effects. However, more long-term studies of treated versus untreated pregnancies are warranted to monitor the safety of treatment and enhance our understanding of the effects of prenatal steroid exposure to the human brain. In the first year of life, optimization of medical treatment in salt-wasting patients is achieved by combining the lowest dose of glucocorticoid able to suppress androgen secretion with the normalization of sodium balance by giving appropriate sodium chloride supplementation.