Ontogenetic pattern of thyroid hormone receptor expression in the human testis

We studied the spatiotemporal distribution of thyroid hormone nuclear recep tors (TRs) alpha(1) and alpha(2) and beta messenger RNA (mRNA) levels in no rmal human testicular tissue during development and in adulthood. Nonpathol ogical specimens from five aborted fetuses (17 and 23 weeks of gestation, t hree and two cases, respectively) and from four patients undergoing orchiec tomy (18 months old and 38-, 42-, and 52-yr-old, respectively) were analyze d by Northern blot, semiquantitative RT-PCR amplification using DNA sequenc es or specifically designed primers for the TR isoforms, and in situ hybrid ization. By using PCR amplification, we found that TRalpha 1 and TRalpha 2 are both expressed at different levels in fetal and adult testis. At all ages TRalph a 2 is found at higher levels. Northern analysis showed hybridization signa ls corresponding to the expression of TRalpha 2 and TRalpha 1 in a ratio th at increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fac t, the expression of TRalpha 1 dramatically decreased throughout developmen t, being faintly detectable in the adult testis. Expression of TRbeta was n ot detected at any age studied. This finding was further confirmed by PCR, which did not amplify TRbeta either in fetal or in adult testis mRNAs. In s itu hybridization studies showed the absence of TRP and that TRalpha 1 and TRalpha 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 ex presses TRalpha, which is localized in Sertoli cells, TRbeta being always u ndetectable. Fetal and prepubertal ages represent the period of maximal exp ression of TRalpha 1 and TRalpha 2. The alpha(2)/alpha(1) ratio rises drama tically after development. These results confirm a critical window for the action of thyroid hormone in human testis, in the period of maximal express ion of T-3 binding isoform TRalpha 1, and may account for the macroorchidis m without virilization occurring when hyposecretion of thyroid hormones occ urs before puberty.