Journal of Endocrinology and Reproduction

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Molecular Mechanism Underlying the Temporal Shift in Androgen Action in Post-Natal Rat Epididymis Due to Gestational-Onset Hypothyroidism


Affiliations
1 Bungtown Road, Cold Spring Harbor Laboratories, Cold Spring Harbor, New York, 11724, United States
2 Department of Biomedical and Diagnostic Sciences, UT College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4550, United States
3 Texas Tech University Health Sciences Centre, 5001 El Paso Dr, Texas, United States
4 Department of Endocrinology, Dr.ALM Post Graduate Institute of Basic Medical Sciences,University of Madras-Taramani Campus, Chennai-600 113, India
     

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Thyroid hormones are important regulators of male fertility and mammalian testis with has specific T3 receptors has emerged as its target. Men with history of congenital or juvenile onset hypothyroidism suffer infertility. The epididymis plays a pivotal role in post-testicular maturation of sperm. Recently we reported that transient gestational–onset hypothyroidism leads to infertility in the progeny of rats by affecting sperm maturation due to decreased androgen receptor (Ar) status in the epididymis. In the present study we tested the hypothesis “transient gestational exposure to antithyroid drugs during critical periods of differentiation of male reproductive tract organs may interfere with the functions of epididymis in F1 progeny by modifying the expression of Ar gene, and activity of its protein and the key steroidogenic enzyme, 5α-reductase”. To test the hypothesis, pregnant rats were exposed to the antithyroid drug methimazole (0.05% through drinking water) from embryonic day (ED)9 to 14/18/21covering specific periods of testicular and other male reproductive tract organs differentiation to induce hypothyroidism. Male pups with transient gestational hypothyroidism showed subnormal levels of serum testosterone, and estradiol, along with decreased expression of Ar, and 5α-reductase activity in the epididymis of pre-puberal rats at postnatal day (PND)29, whereas there was normal/boosted Ar expression, and 5α-reductase activity peripubertal rat epididymis at PND 49. Taken together, the present study and our previous report point out that gestational-onset hypothyroidism affect fertility of F1 progeny through an age-dependent divergent effect on 5α-reductase activity and AR gene expression in the epididymis.

Keywords

Androgen Receptor, Dihydrotestosterone, 5α-Reductase, Testosterone, Thyroid Hormone.
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  • Molecular Mechanism Underlying the Temporal Shift in Androgen Action in Post-Natal Rat Epididymis Due to Gestational-Onset Hypothyroidism

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Authors

Anbalagan Jaganathan
Bungtown Road, Cold Spring Harbor Laboratories, Cold Spring Harbor, New York, 11724, United States
Arokya Mary Sashi
Department of Biomedical and Diagnostic Sciences, UT College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4550, United States
Annapoorna Kannan
Texas Tech University Health Sciences Centre, 5001 El Paso Dr, Texas, United States
Mariajoseph Michael Aruldhas
Department of Endocrinology, Dr.ALM Post Graduate Institute of Basic Medical Sciences,University of Madras-Taramani Campus, Chennai-600 113, India

Abstract


Thyroid hormones are important regulators of male fertility and mammalian testis with has specific T3 receptors has emerged as its target. Men with history of congenital or juvenile onset hypothyroidism suffer infertility. The epididymis plays a pivotal role in post-testicular maturation of sperm. Recently we reported that transient gestational–onset hypothyroidism leads to infertility in the progeny of rats by affecting sperm maturation due to decreased androgen receptor (Ar) status in the epididymis. In the present study we tested the hypothesis “transient gestational exposure to antithyroid drugs during critical periods of differentiation of male reproductive tract organs may interfere with the functions of epididymis in F1 progeny by modifying the expression of Ar gene, and activity of its protein and the key steroidogenic enzyme, 5α-reductase”. To test the hypothesis, pregnant rats were exposed to the antithyroid drug methimazole (0.05% through drinking water) from embryonic day (ED)9 to 14/18/21covering specific periods of testicular and other male reproductive tract organs differentiation to induce hypothyroidism. Male pups with transient gestational hypothyroidism showed subnormal levels of serum testosterone, and estradiol, along with decreased expression of Ar, and 5α-reductase activity in the epididymis of pre-puberal rats at postnatal day (PND)29, whereas there was normal/boosted Ar expression, and 5α-reductase activity peripubertal rat epididymis at PND 49. Taken together, the present study and our previous report point out that gestational-onset hypothyroidism affect fertility of F1 progeny through an age-dependent divergent effect on 5α-reductase activity and AR gene expression in the epididymis.

Keywords


Androgen Receptor, Dihydrotestosterone, 5α-Reductase, Testosterone, Thyroid Hormone.

References





DOI: https://doi.org/10.18519/jer%2F2016%2Fv20%2F149829