We studied the spatiotemporal distribution of thyroid hormone nuclear receptors (TRs) α1 and α2 and β 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(α1) and TR(α2) are both expressed at different levels in fetal and adult testis. At all ages TR(α2) is found at higher levels. Northern analysis showed hybridization signals corresponding to the expression of TR(α2) and TR(α1) in a ratio that increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fact, the expression of TR(α1) dramatically decreased throughout development, being faintly detectable in the adult testis. Expression of TR(β) was not detected at any age studied. This finding was further confirmed by PCR, which did not amplify TR(β) either in fetal or in adult testis mRNAs. In situ hybridization studies showed the absence of TR(β) and that TR(α1) and TR(α2) 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(α), which is localized in Sertoli cells, TR(β) being always undetectable. Fetal and prepubertal ages represent the period of maximal expression of TR(α1) and TR(α2). The α2/α1 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(α1), and may account for the macroorchidism without virilization occurring when hyposecretion of thyroid hormones occurs before puberty.

Ontogenetic pattern of thyroid hormone receptor expression in the human testis

Crescenzi, A;
2000-01-01

Abstract

We studied the spatiotemporal distribution of thyroid hormone nuclear receptors (TRs) α1 and α2 and β 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(α1) and TR(α2) are both expressed at different levels in fetal and adult testis. At all ages TR(α2) is found at higher levels. Northern analysis showed hybridization signals corresponding to the expression of TR(α2) and TR(α1) in a ratio that increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fact, the expression of TR(α1) dramatically decreased throughout development, being faintly detectable in the adult testis. Expression of TR(β) was not detected at any age studied. This finding was further confirmed by PCR, which did not amplify TR(β) either in fetal or in adult testis mRNAs. In situ hybridization studies showed the absence of TR(β) and that TR(α1) and TR(α2) 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(α), which is localized in Sertoli cells, TR(β) being always undetectable. Fetal and prepubertal ages represent the period of maximal expression of TR(α1) and TR(α2). The α2/α1 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(α1), and may account for the macroorchidism without virilization occurring when hyposecretion of thyroid hormones occurs before puberty.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/68007
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