This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Soriano-Guillen, L. Articles by Lahlou, N. Search for Related Content PubMed PubMed Citation Articles by Soriano-Guillen, L. Articles by Lahlou, N. Related Collections Pediatric Endocrinology Male Endocrinology

Activating Mutations in the Luteinizing Hormone Receptor Gene: A Human Model of Non-Follicle-Stimulating Hormone-Dependent Inhibin Production and Germ Cell Maturation

Department of Pediatric Endocrinology (L.S.-G., J.-C.C.), Laboratory of Pathology (P.B.), and the Laboratory for Hormone Biology (M.R., N.L.), Centre Hospitalier Universitaire Cochin, Saint Vincent de Paul, 75014 Paris, France; Department of Endocrinology (L.S.-G.), Hospital Infantil Nino Jesus, 28009 Madrid, Spain; and Laboratory of Spermiology and Histology (V.M.), Centre Hospitalier Régional Universitaire, Faculty of Medicine, 59037 Lille, France

Address all correspondence and requests for reprints to: Dr. Najiba Lahlou, Biologie Hormonale, Hôpital Saint Vincent de Paul, 82 avenue Denfert-Rochereau, 75014 Paris, France. E-mail: najiba.lahlou{at}svp.aphp.fr.

Context: Familial male-limited precocious puberty is a dominant autosomal genetic disease caused by activating LH receptor gene mutations, clinically expressed only in males. In preliminary studies, in addition to the expected testosterone increase, we found high inhibin B levels before the age of normal puberty.

Objectives: The objective of the study was to assess the cellular origin of serum inhibin thanks to testis section immunostaining.

Main Outcome Measures: Serum testosterone, gonadotropin, inhibin B, pan-C-inhibin, and anti-Mullerian hormone levels were measured. Immunostaining was performed using specific anti-- and anti-ß-subunit antibodies.

Subjects and Methods: Five boys from three families (mutation M398T or I542L) were investigated at onset (2–6 yr), on ketoconazole treatment, and at adolescence. Testis biopsies were performed in three subjects before the disease was fully characterized.

Results: The high testosterone levels were suppressed by ketoconazole. Anti-Mullerian hormone levels were inversely related to testosterone: low at diagnosis, elevated after testosterone suppression. Despite FSH suppression, inhibin B and pan-C-inhibin levels were high from clinical onset to adolescence. Biopsy specimens showed normal Sertoli cell complement and germ cell maturation until the spermatocyte II stage. Sertoli and Leydig cells displayed positive inhibin -subunit immunostaining. Only Leydig cells and spermatogonia stained positively for the inhibin ßB-subunit.

Conclusions: Familial male-limited precocious puberty is a unique model of inhibin B secretion, demonstrating that Leydig cells can produce significant amounts of the dimeric molecule. Our results also suggest that the pubertal FSH rise is not required for full expression of the two inhibin B genes and for the initiation of germ cell maturation.

This article has been cited by other articles:

				H. J. Hirsch, T. Eldar-Geva, F. Benarroch, O. Rubinstein, and V. Gross-Tsur Primary Testicular Dysfunction Is a Major Contributor to Abnormal Pubertal Development in Males with Prader-Willi Syndrome J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2262 - 2268. [Abstract] [Full Text] [PDF]

				H. E. Chemes, R. A. Rey, M. Nistal, J. Regadera, M. Musse, P. Gonzalez-Peramato, and A. Serrano Physiological Androgen Insensitivity of the Fetal, Neonatal, and Early Infantile Testis Is Explained by the Ontogeny of the Androgen Receptor Expression in Sertoli Cells J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4408 - 4412. [Abstract] [Full Text] [PDF]

				F. De Luca, V. Mitchell, M. Wasniewska, T. Arrigo, M. F. Messina, M. Valenzise, L. de Sanctis, and N. Lahlou Regulation of spermatogenesis in McCune-Albright syndrome: lessons from a 15-year follow-up. Eur. J. Endocrinol., June 1, 2008; 158(6): 921 - 927. [Abstract] [Full Text] [PDF]

				S. T. Page, J. K. Amory, and W. J. Bremner Advances in Male Contraception Endocr. Rev., June 1, 2008; 29(4): 465 - 493. [Abstract] [Full Text] [PDF]