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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 9 3453-3457
Copyright © 2000 by The Endocrine Society

Original Studies

Ontogenetic Pattern of Thyroid Hormone Receptor Expression in the Human Testis

Emmanuele A. Jannini, Anna Crescenzi, Nadia Rucci, Emiliano Screponi, Eleonora Carosa, Anna De Matteis, Enrico Macchia, Giulia d’Amati and Massimino D’Armiento

Department of Experimental Medicine (E.A.J., N.R., E.S., E.C.), University of L’Aquila, L’Aquila 67100; Institute of Urology (A.D.M.) and Department of Experimental Medicine and Pathology (G.d.A., M.D.A.), University of Rome "La Sapienza", Rome 00161; Department of Endocrinology (E.M.), University of Pisa, Pisa 56124; and Diagnostic Department (A.C.), "Regina Apostolorum" Hospital, Albano Laziale 00041, Italy

Address correspondence and requests for reprints to: Massimino D’Armiento, M.D., Chair of Endocrinology, Department of Experimental Medicine and Pathology, University of Rome "La Sapienza," Policlinico Umberto I–Viale del Policlinico, 155, 00161 Rome, Italy. E-mail: massimino.darmiento{at}uniroma1.it

We studied the spatiotemporal distribution of thyroid hormone nuclear receptors (TRs) {alpha}1 and {alpha}2 and ß messenger RNA (mRNA) levels in normal human testicular tissue during development and in adulthood. Nonpathological specimens from five aborted fetuses (17 and 23 weeks of gestation, three and two cases, respectively) and from four patients undergoing orchiectomy (18 months old and 38-, 42-, and 52-yr-old, respectively) were analyzed by Northern blot, semiquantitative RT-PCR amplification using DNA sequences or specifically designed primers for the TR isoforms, and in situ hybridization.

By using PCR amplification, we found that TR{alpha}1 and TR{alpha}2 are both expressed at different levels in fetal and adult testis. At all ages TR{alpha}2 is found at higher levels. Northern analysis showed hybridization signals corresponding to the expression of TR{alpha}2 and TR{alpha}1 in a ratio that increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fact, the expression of TR{alpha}1 dramatically decreased throughout development, being faintly detectable in the adult testis. Expression of TRß was not detected at any age studied. This finding was further confirmed by PCR, which did not amplify TRß either in fetal or in adult testis mRNAs. In situ hybridization studies showed the absence of TRß and that TR{alpha}1 and TR{alpha}2 colocalized in Sertoli cells of prepubertal testis, whereas germ and interstitial cells appeared devoid of TR mRNA signals.

From these results it can be concluded that the human testis exclusively expresses TR{alpha}, which is localized in Sertoli cells, TRß being always undetectable. Fetal and prepubertal ages represent the period of maximal expression of TR{alpha}1 and TR{alpha}2. The {alpha}2/{alpha}1 ratio rises dramatically after development. These results confirm a critical window for the action of thyroid hormone in human testis, in the period of maximal expression of T3 binding isoform TR{alpha}1, and may account for the macroorchidism without virilization occurring when hyposecretion of thyroid hormones occurs before puberty.




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