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This version published online on March 14, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1925
A more recent version of this article appeared on June 1, 2006
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Submitted on August 29, 2005
Accepted on March 6, 2006

Nerve Growth Factor-Dependent Activation of trkA Receptors in the Human Ovary Results in Synthesis of FSH Receptors and Estrogen Secretion

C Salas, M Julio-Pieper, M Valladares, R Pommer, M Vega, C Mastronardi, B Kerr, S R Ojeda, H E Lara, and C Romero*

Laboratorio de Endocrinología Biología Reproductiva, Depto de Obstetricia y Ginecología, Hospital Clínico JJ Aguirre, Santiago, Chile; Instituto de Investigaciones Materno Infantil (IDIMI), Escuela de Medicina, Universidad de Chile, Santiago, Chile; Oregon National Primate Research Center, Beaverton, OR, USA; Laboratorio de Neurobioquímica, Depto. Bioquímica y Biología Molecular, Fac. de Ciencias Quimicas y Farmacéuticas, Universidad de Chile, Santiago, Chile

* To whom correspondence should be addressed. E-mail: cromero{at}ns.hospital.uchile.cl.

Context: Earlier studies showed that nerve growth factor (NGF) induces the expression of functional FSH receptors (FSHR) in preantral follicles of the developing rat ovary.

Objective: We studied if NGF can affect granulosa cell (GC) function in human periovulatory follicles using intact human ovaries and isolated human GCs.

Patients and Interventions: Human GCs were obtained from IVF patients and normal ovaries from women with elective pelvic surgery for non-ovarian indications.

Results: In normal ovaries, NGF and trkA (NGF's high-affinity receptor), were detected by immunohistochemistry in GCs of preantral and antral follicles. NGF and trkA are also present in theca cells of antral follicles. Both freshly collected and cultured GCs contained immunoreactive NGF and trkA, in addition to their respective mRNAs. Human GCs respond to NGF with increased estradiol (E2) secretion and a reduction in progesterone (P) output. Exposure of human GCs to NGF increased FSHR mRNA content within 18 h of treatment, and this effect was blocked by trk tyrosine kinase blocker K-252a. Also, cells pre-exposed to NGF released significantly more E2 in response to hFSH than cells not pretreated with the neurotrophin, showing that NGF-induced increase in FSHR gene expression results in the formation of functional FSHRs.

Conclusions: These results suggest that one of the functions of NGF in the preovulatory human ovary is to increase the secretion of E2, while preventing early luteinization via an inhibitory effect on P secretion. NGF stimulates E2 secretion both directly and by increasing the formation of FSH receptors.
Key words: NGF • TrkA receptor • FSH receptor • steroids • human granulosa cells




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