title: Effect of neonatal hypothyroidism on prepubertal mouse testis in relation to thyroid hormone receptor alpha 1 (THRα1).
abstract: Thyroid hormones (THs) are important for growth and development of many tissues, and altered thyroid status affects various organs and systems. Testis also is considered as a thyroid hormone responsive organ. Though THs play an important role in regulation of testicular steroidogenesis and spermatogenesis, the exact mechanism of this regulation remains poorly understood. The present study, therefore, is designed to examine the effect of neonatal hypothyroidism on prepubertal Parkes (P) strain mice testis in relation to thyroid hormone receptor alpha 1 (THRα1). Hypothyroidism was induced by administration of 6-propyl-2-thiouracil (PTU) in mother's drinking water from birth to day 28; on postnatal day (PND) 21 only pups, and on PND 28, both pups and lactating dams were euthanized. Serum T3and T4were markedly reduced in pups at PND 28 and in lactating mothers, while serum and intra-testicular testosterone levels were considerably decreased in pups of both age groups. Further, serum and intra-testicular levels of estrogen were significantly increased in hypothyroid mice at PND 28 with concomitant increase in CYP19 expression. Histologically, marked changes were noticed in testes of PTU-treated mice; immunohistochemical and western blot analyses of testes in treated mice also revealed marked decrease in the expression of THRα1 at both age groups. Semiquantitative RT-PCR and western blot analyses also showed reductions in both testicular mRNA and protein levels of SF-1, StAR, CYP11A1 and 3β-HSD in these mice. In conclusion, our results suggest that neonatal hypothyroidism alters localization and expression of THRα1 and impairs testicular steroidogenesis by down-regulating the expression SF-1, thereby affecting spermatogenesis in prepubertal mice.
authors: Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
authors: Debarshi
authors: D
authors: Sarkar
authors: Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address: shioks@rediffmail.com.
authors: Shio Kumar
authors: SK
authors: Singh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D005260:Female; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011441:Propylthiouracil / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012741:Sexual Maturation; D013256:Steroids / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D013256:Steroids; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D011441:Propylthiouracil
keywords: Hypothyroidism; Mouse; SF-1; Spermatogenesis; THRα1; Testicular steroidogenesis