Transient Neonatal-Onset Hypothyroidism Boosts Estradiol Synthesis in the Testis of Adult Wistar Rat

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Authors

  • N. S. Venkatesh
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN
  • M. Kathiresh Kumar
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN
  • S. Sambavi
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN
  • N. Kalpana
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN
  • A. M. Sashi John
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN
  • J. Anbalagan
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN
  • R. Ilangovan
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN
  • M. M. Aruldhas
     Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113 ,IN

Keywords:

Leydig Cells, Sertoli Cells, LHR, FSHR, Hypothyroidism.

Abstract

Transient neonatal hypothyroidism is known to boost Sertoli cell (SC), Leydig cell (LC) and germ cell (GC) number at adult age. Existing reports attribute decreased steroidogenic potential of LCs to unaltered/decreased serum testosterone in such rats, despite a boost in the cell number. However, these studies have ignored the status of estradiol in such conditions. In this present study, we tested the hypothesis "transient neonatal-onset hypothyroidism may lead to a temporal shift in adult rat testicular steroidogenesis towards estradiol production". Hypothyroidism was induced in neonates by providing methimazole (MMI) in drinking water (0.05%) to lactating mothers and pups for a transient period from postnatal day 1 (PND 1) to PND 14 or from PND 1 to PND 29. After the experimental period, the pups were provided drinking water free of MMI and sacrificed on PND 91. Coeval rats without MMI exposure served as control. Radioimmunoassay revealed decreased serum titres of luteinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH) and prolactin (PRL); while serum testosterone remained unaltered, its level in testicular interstitial fluid (TIF) decreased. Between the two major metabolites of testosterone, 5α-dihydrotestosterone (DHT) concentration decreased in serum and TIF, whereas estradiol recorded a significant increase in both. Transient neonatal-onset hypothyroidism decreased 3β-hydroxy steroid dehydrogenase (3β-HSD) in LCs but augmented 17β-HSD activity. Radio-receptor assay revealed decreased concentration of LHR and ER in LCs of hypothyroid groups, whereas AR and PRLR increased. While aromatase activity decreased in LCs, it increased along with FSHR in SCs, when compared to control rats. The changes in LHR and FSHR levels and aromatase were consistent with the expression level of the respective genes. The present study supports the proposed hypothesis and suggests that transient neonatal-onset hypothyroidism-induced boost in estradiol in adult rat testis may be due to augmented expression and activity of aromatase, and FSHR content in SCs of these rats.

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Published

2015-06-01

How to Cite

Venkatesh, N. S., Kathiresh Kumar, M., Sambavi, S., Kalpana, N., Sashi John, A. M., Anbalagan, J., Ilangovan, R., & Aruldhas, M. M. (2015). Transient Neonatal-Onset Hypothyroidism Boosts Estradiol Synthesis in the Testis of Adult Wistar Rat. Journal of Endocrinology and Reproduction, 18(2), 95–110. Retrieved from http://www.informaticsjournals.com/index.php/jer/article/view/1890

Issue

Volume 18, Issue 2, December 2014

Section

Articles

 

References

Abney TO. (1999) The potential roles of estrogens in regulating Leydig cell development and function: A review. Steroids 64: 610-17.

Akingbemi BT, Ge RS, Hardy MP. (1999) Leydig cells. In: Knobil E, Neill JD (Eds.), Encyclopedia of Reproduction. Vol 3, pp 1021-33. London: Academic Press.

Aldred LF, Cooke BA. (1983) The effect of cell damage on the density and steroidogenic capacity of rat testis Leydig cells using an NADH exclusion test for determination of viability. J Steroid Biochem. 18: 411-14.

Anderson S. (1995) 17β-hydroxysteroid dehydrogenase: isozymes and mutations. J Endocrinol. 146: 197-200.

Ando S, Panno ML, Beraldi E, Tarandino G, Salerno M, Palmero S, Prati M, Fugassa E. (1990) Influence of hypothyroidism on in vitro testicular steroidogenesis in adult rats. Exp Clin Endocrinol. 96: 149-56.

Antony FF, Aruldhas MM, Udhayakumar RCR, Maran RRM, Govindarajulu P. (1995) Inhibition of Leydig cell activity in vivo and in vitro in hypothyroid rats. J Endocrinol. 144: 293-300.

Ariyaratne HBS. Mendis-Handagama SMLC, Hales BD, Mason IJ (2000) Studies on the onset of Leydig precursor cell differentiation in the prepubertal rat testis. Biol Reprod. 63: 165-71.

Ariyaratne HBS, Mendis-Handagama SMLC, Mason JI. (2000b) Effects of tri-iodothyronine on testicular interstitial cells and androgen secretory capacity of the prepuberal rat. Biol Reprod. 63: 493-502.

Ariyaratne HBS, Mills N, Mason JI, Mendis-Handagama SMLC. (2000c) Effects of thyroid hormone on Leydig cell regeneration in adult rat following ethane dimethane sulphonate treatment. Biol Reprod. 63: 1115-23.

Aruldhas MM. (2002) Thyroid and the mammalian testis – An update. In: Akbarsha MA (Ed.), Proceedings of XX Symposium on Reproductive Biology and Comparative Endocrinology. pp. 15-18. Tiruchirappalli, India: Bharathidasan University.

Aruldhas MM, Ramalingam N, Jaganathan A, John Sashi AM, Stanley JA, Nagappan AS, Vasavan J, Kannan A, Seshadri VN. (2010) Gestational and neonatal-onset hypothyroidism alters androgen receptor status in rat prostate glands at adulthood. Prostate 70: 689-700.

Banu,SK, Govindarajulu P, Aruldhas MM.. (2002) Developmental profiles of TSH, sex steroids, and their receptors in the thyroid and their relevance to thyroid growth in immature rats. Steroids 67:137-44.

Bartlett JMS, Chariton HM, Robinson ICAF, Nieschlag E. (1990) Pubertal development and testicular function in the male growth hormone deficient rat. J Endocrinol. 126: 193-201.

Bergmeyer MU. (1974) Steroid dehydrogenase. In: Bergmeyer MU (Ed.), Methods of Enzymatic Analysis, Vol. I, pp. 476-77. New York: Academic Press.

Brown TR. (1999) Androgen metabolism and action. In: Wang C (ed.), Male Reproductive Function. pp. 65-84. London: Kluwer Academic Publishers.

Burger HG. (2001) Gonadal regulatory peptides. In: De Groot LJ, Jameson JL (Eds.), Endocrinology, Vol. III, 4th Edition, pp. 1905-15. London: WB.Saunders Company.

Bousfield GR, Perry WM, Ward DN. (1994) Gonadotrophins: chemistry and biosynthesis. In: Knobil E, Neill JD (Eds.), The Physiology of Reproduction. pp. 1749-92. New York: The Raven Press.

Christensen AK, Fawcett DW. (1966) The fine structure of testicular interstitial cells in mice. Am J Anat. 118: 55171.

Cooke PS. (1995) Role of thyroid hormones in Sertoli cell mitogenesis and differentiation. Mol Androl. 7: 178-89.

Cooke PS, Meisami E. (1991) Early hypothyroidism in rats causes increased adult testis and reproductive organ size but does not change testosterone levels. Endocrinology 129: 237-43.

Cooke PS, Porcelli J, Hess RA. (1992) Induction of increased testis growth and sperm production in adult rats by neonatal administration of the goitrogen propylthiouracil (PTU): the critical period. Biol Reprod. 46: 146-54.

Cooke PS, Kirby JD, Porcelli J. (1993). Increased testis growth and sperm production in adult rats following transient neonatal goitrogen treatment: optimization of the propylthiouracil dose and effects of methimazole. J Reprod Fertil. 97: 493-99.

de Kretser DM, Kerr JB. (1994) The cytology of the testis. In: Knobil E, Neill JD (Eds), The Physiology of Reproduction, pp. 1177-1290. New York: The Raven Press. .

Dufau ML. (1988).Endocrine regulation and communicating functions of the Leydig cell. Ann Rev Physiol. 50: 483508.

Duan WR, Parmer TG, Albarracin CT, Zhong L, Gibori G. (1997) PRAP, a prolactin receptor associated protein: its gene expression and regulation in the corpus luteum. Endocrinology 138: 3216-21.

Freeman DA. (1985) Estradiol acts as a competitive inhibitor of the 3 beta-hydroxysteroid dehydrogenase/delta 5delta 4 isomerase enzyme of cultured Leydig tumor cells. Endocrinology 117: 2127-33.

Furuya T. (1990) Onset of compensatory hypertrophy of interstitial tissue and Leydig cells in rats hemicastrated around the time of puberty. Biol Reprod. 42: 491-98.

Hall PF. (1994). Testicular steroid synthesis: Organization and regulation. In: Knobil E, Neill JD (Eds.), The Physiology of Reproduction, pp. 1335-62. New York: The Raven Press.

Hardy MP, Kirby JD, Hess RA, Cooke PS. (1993) Leydig cells increase their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. Endocrinology 132: 2417-20.

Haynes RCJ. (1991) Thyroid and antithyroid drugs. In: Gillman AG,

Rall TW, Nies AS, Taylor P (Eds.), The Pharmacological Basis of Therapeutics, Vol. II, 8th edition. pp. 1373-1375. Singapore: Pergamon Press.

Hermanns SU, Hafez ESE. (1981) Prolactin and male reproduction. Systems Biol Reprod Med. 6: 91-125.

Huhtaniemi IT. (1999) Endocrine regulation of male reproduction. In: Wang C (Ed.), Male Reproductive Function, pp. 1-8. Kluwer Academic Publishers.

Jannini EA, Ulisse S, D'Armiento M. (1995) Thyroid hormone and male gonadal function. Endocr Rev. 16: 443-59.

Jannini EA, Carosa E, Rucci N, Screponi E, D'Armiento M. (1999) Ontogeny and regulation of variant thyroid hormone receptor isoforms in developing rat testis. J Endocrinol Invest. 22: 843-48.

Lillie RD, Fullmer HM. (1976) Histopathologic Technique and Practical Histochemistry, 4th Edition, pp. 559-600. New York: McGraw-Hill.

Longcope C. (2000). The male and female reproductive systems in hypothyroidism. In: Braverman LE, Utiger RD (Eds.), Werner and Ingbar's, The Thyroid, 8th ed, pp. 824–28. Philadelphia: Lippincott Williams & Wilkins..

Maran RRM, Aruldhas MM. (2002) Adverse effects of neonatal hypothyroidism on Wistar rat spermatogenesis. Endocr Res. 28: 141-54.

Maran RRM, Ravisankar B, Ravichandran K, Valli G, Arunakaran J, Aruldhas MM. (1999a) Impact of neonatal onset hypothyroidism on Sertoli cell number, plasma and testicular interstitial fluid androgen binding protein concentration. Endocr Res. 25: 307-22.

Maran RRM, Sivakumar R, Arunakaran J, Ravisankar B, Ravichandran K, Siddharthan V, Jeyaraj DA, Aruldhas MM. (1999b) Duration-dependent effect of transient neonatal hypothyroidism on Sertoli and germ cell number, and plasma and testicular interstitial fluid androgen binding protein concentration. Endocr. Res. 25: 323-40.

Maran RRM, Arunakaran J, Jeyaraj DA, Ravichandran K, Ravisankar B, Aruldhas MM. (2000) Transient neonatal hypothyroidism alters plasma and testicular sex steroid concentration in puberal rats. Endocr Res. 26: 41129.

Maran RRM, Arunakaran J, Aruldhas MM. (2001) Prolactin and Leydig cells: Biphasic effects of prolactin on LH, T3 and GH-induced testosterone / estradiol secretion by Leydig cells in puberal rats. Int J Androl. 24: 48-55.

Mendis-Handagama SMLC. (2012) Neonatal-prepubertal hypothyroidism on postnatal testis development. In: Springer D (Ed.), A New Look at Hypothyroidism, ISBN: 978-953-51-0020-1, DOI: 10.5772/1215, pp. 209-228. Croatia: InTech Open Access.

Mendis-Handagama SMLC, Ariyaratne HB. (2001) Differentiation of the adult Leydig cell population in the postnatal testis. Biol Reprod. 65: 660-71.

Mendis-Handagama SMLC, Sharma OP. (1994) Effects of neonatal administration of the reversible goitrogen propylthiouracil on the testis interstitium in adult rats. J Reprod Fertil. 100: 85-92.

Mori H, Christensen AK. (1980) Morphometric analysis of Leydig cells in the normal rat testis. J Cell Biol. 84: 34054.

Nokelainen P, Peltoketo H, Vihko R, Vihko P. (1998) Expression cloning of a novel estrogenic mouse 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase, previously described as a prolactin receptor-associated protein (PRAP) in rat. Mol Endocrinol. 12: 1048-59.

O'Shaughnessy PJ, Baker PJ, Heikkila M, Vainio S, McMahon AP. (2000) Localization of 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase isoform expression in the developing mouse testis – androstenedione is the major androgen secreted by fetal/neonatal Leydig cells. Endocrinology 141: 2631-37.

Palmero S, De Marco P, Fugassa E. (1995) Thyroid hormone receptor beta mRNA expression in Sertoli cells isolated from prepuberal testis. J Mol Endocrinol. 14: 131-34.

Panno ML, Sisco D, Salerno M, Lanzino M, Pezzi V, Morrone EG, Mauro L, Palmero S, Fugassa E, Ando S. (1996) Thyroid hormone modulates androgen and estrogen receptor content in the Sertoli cells of peripubertal rats. J Endocrinol. 148: 43-60.

Russell LD, Ettlin RA, Sinha Hikim AP, Clegg ED. (1990) Histological and histopathological evaluation of the testis. In: Russell LD, Griswold MD (Eds.), The Sertoli Cell, pp. 38-59. Clearwater, Florida: Cache River Press.

Saez JM. (1994) Leydig cells: Endocrine, paracrine and autocrine regulation. Endocr Rev. 15: 574-626.

Sufi S, Donaldson A, Jeffcoate S. (1999) WHO matched reagent, programme steroid radioimmunoassay method manual. Pp. 36-46. Geneva: WHO.

Setchell BP, Maddocks S, Brooks DE. (1994) Anatomy, vasculature innervation and fluids of male reproductive tract. In: Knobil E, Neill JD (Eds.), The Physiology of Reproduction, 2nd edition. pp. 1063-175. New York: The Raven Press.

Tang TK, Bartke A, Gardiner CS, Wagner TE, Yun JS. (1993) Gonadotropin secretion, synthesis and gene expression in human growth hormone transgenic mice and in Ames dwarf mice. Endocrinology 132: 2518-24.

Ulisse S, Jannini EA, Carosa E, Pieranti D, Graziano FM, D'Armiento M. (1994) Inhibtion of aromatase activity in rat Sertoli cells by thyroid hormone. J Endocrinol. 140: 431-36.

Vale W, Bilezikjian LM, Rivier C. (1994) Reproduction and other roles of inhibins and activins. In: Knobil E, Neill JD (Eds.), The Physiology of Reproduction, pp. 1861-78. New York: The Raven Press.

Valle LBS, Oliveira-Filho RM, Romaldini JH, Lara PF. (1985) Pituitary-testicular axis abnormalities in immature male hypothyroid rats. J Steroid Biochem. 23: 253-57.

Venkatesh NS. (2004) Temporal shift in adult rat testicular steroidogenesis towards estradiol due to transient neonatal hypothyroidism. Ph.D. thesis, Chennai, India: University of Madras.

Walker WH. (2009) Molecular mechanisms of testosterone action in spermatogenesis. Steroids 7: 602-07.

Yu WH, Kimura M, Walczewska A, Karanth S, McCann SM. (1997) Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci USA. 94: 1023-28.

Zirkin BR. (1995a) What is the relationship between the various endocrine components of the male reproductive system Hypothalamo-pituitary-testicular axis, feedback loops. In: Robaire B, Pryor JL, Trasler JM (Eds.), The Handbook of Andrology, pp. 5-7. Allen Press Inc., Lawrence: The American Society of Andrology.

Zirkin BR. (1995b) What compounds mediate communication within the male reproductive system Where and how are male-associated hormones produced Gonadotrophins, steroids and their sites of synthesis. In: Robaire B, Pryor JL, Trasler JM (Eds.), The Handbook of Andrology, pp. 8-9. Allen Press Inc., Lawrence: The American Society of Andrology.

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