Testis

Regulation of Neonatal Sertoli Cell Development by Thyroid Hormone Receptor 1

Abstract
Neonatal hypothyroidism increases adult Sertoli cell populations by extending Sertoli cell proliferation. Conversely, hyperthyroidism induces premature cessation of Sertoli cell proliferation and stimulates maturational events like seminiferous tubule canalization. Both thyroid hormone receptor alpha 1 (THRA1) and beta 1 (THRB1), which are commonly referred to as TR1 and TR1, respectively, are expressed in neonatal Sertoli cells. We determined the relative roles of TR1 and TR1 in the thyroid hormone effect on testicular development and Sertoli cell proliferation using Thra knockout (TRKO), Thrb knockout (TRKO) and wild-type (WT) mice. Triiodothyronine (T3) treatment, from birth until postnatal day 10 reduced Sertoli cell proliferation to minimal levels in WT and TRKO mice versus their untreated controls, whereas T3 had a diminished effect on TRKO Sertoli cell proliferation. Seminiferous tubule patency and luminal diameter were increased in T3-treated WT and TRKO testes. In contrast, T3 had no effect on these parameters in TRKO mice. In untreated adult TRKOs, Sertoli cell number, testis weight and daily sperm production were increased or trended toward an increase, although the increase in magnitude was smaller than in WT mice following neonatal hypothyroidism. Conversely, in TRKO mice, Sertoli cell number, testis weight and daily sperm production were similar to untreated WT mice. In addition, Sertoli cell number and testis weight in adult WT and TRKO mice showed comparable increases following hypothyroidism. Our results show that TRKO mice have testicular effects similar to those seen in WT mice following neonatal hypothyroidism, and that TRKO mice, but not TRKOs, have normal Sertoli cell responsiveness to T3. Thus, T3 effects of exogenous manipulation of T3 on neonatal Sertoli cell development are predominately mediated through TR1.

Key words: Testis • Sertoli cells

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