Skip to main content
SpringerLink
Log in

Effect of thyroid hormone on the development and gene expression of hormone receptors in rat testes in vivo

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Thyroid hormone is known to play a pivotal role in the regulation of prepuberal rat testes development and function with specific influence on the differentiation of Sertoli cells, the only cell type that expresses thyroid hormone receptors in testes. To explore in vivo effects of thyroid hormone on testes development and the regulation of testicular gene expression, the hyperand hypothyroid rat models were established by T3 injection to pups (ip 100 μg/kg bw) and by oral administration of 6-N-propyl-2-thiouracil (PTU) to the lactating mother from days 1 to 21 post-delivery. Half of the rats from each group were sacrificed at 21 days of age, and the other half were allowed to recover with discontinued treatments from day 22 to day 50. At 21 days of age, a significantly elevated serum T3 level was observed in hyperthyroid rats (179.5 ng/dl) vs controls (97.5 ng/dl), and in hypothyroid rats a significantly lower level of T3 was detected (26.1 ng/dl). However, serum T4 concentration was significantly lower in both hyper- (0.105 μg/dl) and hypothyroid (0.058 μg/dl) rats compared to the controls (2.48 μg/dl). In recovered rats in which the serum T3 and T4 were restored to normal, the serum T levels remained remarkably lower in both hyper- and hypothyroid rats. The significantly decreased body and testes weights observed in both hyper- and hypothyroid rats at 21 days of age were not restored by the time they were 50 days old. Histological analyses of testes of 21-day-old hypothyroid rats revealed smaller-sized seminiferous tubules, incomplete lumen formation and delayed germ cell differentiation and in hyperthyroid rats an increased number of early stage spermatocytes was found. Testicular mRNA levels of follicle-stimulating hormone receptor (FSH-R), luteinizing hormone receptor (LH-R) and androgen binding protein (ABP) were studied by Northern blot hybridization. At 21 days of age data showed that FSH-R mRNA levels were significantly higher in both hyper- and hypothyroid rat testes compared to controls, but no differences were detected in recovered 50-day-old rats. Significantly decreased ABP mRNA levels were detected only in hypothyroid rat testes compared to those in both the hyperthyroid and control groups at 21 days of age, but no significant change was observed in recovered 50-day-old rats. To further evaluate the effect of thyroid hormone on the Leydig cell function, the 2.3/2.6 kb specific LH-R hybridization bands were detected with rat LH-R cRNA probe. Significant suppression of LH-R mRNA levels was only observed in the hypothyroid rat testes at 50 days of age. The testicular thyroid hormone receptors (TRs) and the regulation of TR by thyroid hormone were investigated using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assays. Both TRα and TRβ mRNAs were identified in the testes from 21- and/or 50- day-old rats. TRα mRNA levels were significantly increased in hypothyroid rat testes and were suppressed in hyperthyroid rats at 21 days of age and no changes of TRα mRNA were found in recovered animals. Our in vivo data strongly suggest that the thyroid hormone directly affects the development of prepuberal testes and the regulation of FSH-R and ABP gene expression in Sertoli cells, as well as the LH-R mRNA levels in Leydig cells, which may lead to further modulating the effect of gonadotropins on testes function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Goldman S., Dirnfeld M., Abramovici H., Kraiem Z. Triiodothyronine (T3) modulates hCG-regulated progesterone secretion, cAMP accumulation and DNA content in cultured human luteinized granulosa cells. Mol. Cell. Endocrinol. 1993, 96: 125–131.

    Article  PubMed  CAS  Google Scholar 

  2. Van Voorhis B.J., Neff T.W., Syrop C.H., Chapler F.K. Primary hypothyroidism associated with multicystic ovaries and ovarian torsion in an adult. Obstet. Gynecol. 1994, 83: 885–887.

    PubMed  Google Scholar 

  3. Jannini E.A., Carosa E., Rucci N., Screponi E., D’Armiento M. Ontogeny and regulation of variant thyroid hormone receptor isoforms in developing rat testis. J. Endocrinol. Invest. 1999, 22: 843–848.

    Article  PubMed  CAS  Google Scholar 

  4. Jannini E.A., Dolci S., Ulisse S., Nikodem V.M. Developmental regulation of the thyroid hormone receptor α 1 mRNA expression in the rat testes. Mol. Endocrinol. 1994, 8: 89–96.

    PubMed  CAS  Google Scholar 

  5. Arambepola N.K., Bunick D., Cooke P.S. Thyroid hormone and follicle-stimulating hormone regulate mullerian inhibiting substance messenger ribonucleic acid expression in cultured neonatal rat Sertoli cells. Endocrinology 1998, 139: 4489–4495.

    PubMed  CAS  Google Scholar 

  6. Ando S., Sirianni R., Forastieri P., et al. Aromatase expression in prepuberal Sertoli cells: effect of thyroid hormone. Mol. Cell. Endocrinol. 2001, 178: 11–21.

    Article  PubMed  CAS  Google Scholar 

  7. Heckert L.L., Griswold M.D. Expression of follicle-stimulating hormone receptor mRNA in rat testes and Sertoli cells. Mol. Endocrinol. 1991, 5: 670–677.

    Article  PubMed  CAS  Google Scholar 

  8. Tena-Sempere M., Zhang F.P., Huhtaniemi I. Persistent expression of a truncated form of the luteinizing hormone receptor messenger ribonucleic acid in the rat testes after selective Leydig cell destruction by ethylene dimethane sulfonate. Endocrinology 1994, 135: 1018–1024.

    PubMed  CAS  Google Scholar 

  9. Anthony C.T., Danzo B.J., Orgebin-Crist M.C. Investigations on the relationship between sperm fertilizing ability and androgen-binding protein in the hypophysectomized, pregnenoloneenolone-injected rat. Endocrinology 1984, 114: 1419–1425.

    Article  PubMed  CAS  Google Scholar 

  10. Holland M.K., Rogers B.J., Orgebin-Crist M.C., Danzo B.J. Effects of photoperiod on androgen-binding protein and sperm fertilizing ability in the hamster. J. Reprod. Fertil. 1987, 81: 99–112.

    Article  PubMed  CAS  Google Scholar 

  11. Majdic G., Sno J., Horvat A., Mrkun J., Kosec M., Cestnik V. Higher thyroid hormone levels in neonatal life result in reduced testis volume in postpubertal bulls. Int. J. Androl. 1998, 21: 352–357.

    Article  PubMed  CAS  Google Scholar 

  12. Kirby J.D., Jetton A.E., Cooke P.S., et al. Developmental hormonal profiles accompanying the neonatal hypothyroidism-induced increase in adult testicular size and sperm production in the rat. Endocrinology 1992, 131: 559–565.

    PubMed  CAS  Google Scholar 

  13. Tamasy V., Du j-Zm Vallerga A., Meisami E., Timiras P.S. Suckling ability and maternal prolactin levels in hypothyroid rats. Horm. Behav. 1984, 18: 457–464.

    Article  PubMed  CAS  Google Scholar 

  14. Trainer T.D. Histology of the normal testes. Am. J. surgical. Pathol. 1987, 11: 797–809.

    Article  CAS  Google Scholar 

  15. Cooke P.S., Meisami E. Early hypothyroidism in rats causes increased adult testes and reproductive organ size but does not change testosterone levels. Endocrinology 1991, 129: 237–243.

    Article  PubMed  CAS  Google Scholar 

  16. Rao J.N., Chandrashekar V., Borg K.E., Bartke A. Effects of photoperiod on testicular inhibin-a and androgen binding protein mRNA expression during postnatal development in Siberian hamsters, Phodopus sungorus. Life Sci. 1995, 57: 1761–1770.

    Article  PubMed  CAS  Google Scholar 

  17. Juszczak M., Steger R.W., Debeljuk L., et al. The effects of short-photoperiod, pinealectomy and melatonin treatment on oxytocin synthesis and release in the male Syrian hamster. Endocrine 1996, 4: 223–231.

    Article  PubMed  CAS  Google Scholar 

  18. Chomaczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 1987, 162: 156–159.

    Google Scholar 

  19. Lad R.P., Smith M.A., Hilt D.C. Molecular cloning and regional distribution of rat brain cyclophilin. Mol. Brain Res. 1991, 9: 239–244.

    Article  PubMed  CAS  Google Scholar 

  20. El-Husseini A.E.D., Paterson J.A., Shiu R.P.C. Basic fibroblast growth factor (BFGF) and two of its receptors, FGFR1 and FGFR2: gene expression in the rat brain during postnatal development as determined by quantitative RTPCR. Mol. Cell Endocrinol. 1994, 104: 191–200.

    Article  Google Scholar 

  21. Sheflin L.G., Fucile N.W., Ozawa S., Spaulding S.W. Thyroxine increases the levels of epidermal growth factor messenger ribonucleic acid (EGF mRNA) in the thyroid in vivo, as revealed by quantitative reverse transcription polymerase chain reaction with an internal control EGF mRNA. Endocrinology 1993, 132: 2319–2324.

    PubMed  CAS  Google Scholar 

  22. Bruni J.F., Marshall S., Dibbet J.A., Meites J. Effects of hyper and hypothyroidism on serum LH and FSH levels in intact and gonadectomized male and female rats. Endocrinology 1975, 97: 558–563.

    Article  PubMed  CAS  Google Scholar 

  23. Ruiz M., Diego A.M., Reyes A., Alonso A., Morell M. Influence of thyroidectomy on serum and pituitary FSH in control and orchidectomized rats. Res. Exp. Med. (Berl.) 1989, 189: 85–90.

    Article  CAS  Google Scholar 

  24. Hardy M.P., Kirby J.D., Hess R.A., Cooke P.S. Leydig cells increase their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism. Endocrinology 1993, 132: 2417–2420.

    PubMed  CAS  Google Scholar 

  25. Baksi S.N. Effect of propylthiouracil-induced hypothyroidism on serum levels of luteinizing hormone and follicle-stimulating hormone in the rat. J. Endocrinol. 1973, 59: 655–656.

    Article  PubMed  CAS  Google Scholar 

  26. Aruldhas M.M., Valivullah H.M., Govindarajulu P. Specific effect of thyroid hormone testicular enzymes involved in carbohydrate metabolism. Biochem. Biophys. Acta 1982, 715: 121–125.

    Article  PubMed  CAS  Google Scholar 

  27. Panno M.L., Salerno M., Lanzino M., et al. Follow-up study on the effects of thyroid hormone administration on androgen metabolism of peripubertal rat Sertoli cells. Eur. J. Endocrinol. 1995, 132: 236–241.

    Article  PubMed  CAS  Google Scholar 

  28. Valle L.B.S., Oliveira-Filho R.M., Romaldini J.H., Lara P.F. Pituitary-testicular axis abnormalities in immature male hypothyroid rats. J. Steroid Biochem. 1985, 23: 253–257.

    Article  PubMed  CAS  Google Scholar 

  29. Van Haaster L.H., De Jong F.H., Docter R., De Rooij D.G. The effect of hypothyroidism on Sertoli cell proliferation and differentiation and hormone levels during testicular development in the rat. Endocrinology 1992, 131: 1574–1576.

    PubMed  Google Scholar 

  30. Palmero S., Prati M., Bolla F., Fugassa E. Tri-iodothyronine directly affects rat Sertoli cell proliferation and differentiation. J. Endocrinol. 1995, 145: 355–362.

    Article  PubMed  CAS  Google Scholar 

  31. Maran R.R., Sivakumar R., Arunakaran J., et al. Durationdependent effect of transient neonatal hypothyroidism on Sertoli and germ cell number, and plasma and testicular interstitial fluid androgen binding protein concentration. Endocr. Res. 1999, 25: 323–340.

    Article  PubMed  CAS  Google Scholar 

  32. French F.S., Ritzen E.M. A high affinity androgen binding protein (ABP) in rat testes: evidence for secretion into efferent duct fluid and absorption by epididymis. Endocrinology 1973, 93: 88–95.

    Article  PubMed  CAS  Google Scholar 

  33. Fugassa E., Palmero S., Gallo G. Triiodothyronine decreases the production of androgen binding globulin by rat Sertoli cells. Biochem. Biophys. Res. Commun. 1987, 143: 241–247.

    Article  PubMed  CAS  Google Scholar 

  34. Hess R.A., Cooke P.S., Bunick D., Kirby J.D. Adult testicular enlargement induced by neonatal hypothyroidism is accompanied by increased Sertoli and germ cell numbers. Endocrinology 1993, 132: 2607–2613.

    PubMed  CAS  Google Scholar 

  35. Palmero S., Maggiani S., Fugassa E. Nuclear triiodothyronine receptors in rat Sertoli cells. Mol. Cell Endocrinol. 1988, 58: 253–256.

    Article  PubMed  CAS  Google Scholar 

  36. Jannini E.A., Olivieri M., Francavilla S., Gulino A., Ziparo E., D’Armiento M. Ontogenesis of the nuclear 3,5,3’-triiodothyronine receptor in the rat testes. Endocrinology 1990, 126: 521–2526.

    Article  Google Scholar 

  37. Evans R.M. The steroid and thyroid hormone receptor superfamily. Science 1988, 240: 889–895.

    Article  PubMed  CAS  Google Scholar 

  38. Lazar M.A. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr. Rev. 1993, 14: 184–193.

    PubMed  CAS  Google Scholar 

  39. Palmero S., De Marco P., Fugassa E. Thyroid hormone receptor β mRNA in Sertoli cells isolated from prepuberal testes. J. Endocrinol. 1995, 14: 131–134.

    Article  CAS  Google Scholar 

  40. Bunick D., Kirby J., Hess R.A., Cooke P.S. Developmental expression of testes messenger ribonucleic acids in the rat following prophylthiouracil-induced neonatal hypothyroidism. Biol. Reprod. 1994, 51: 706–713.

    Article  PubMed  CAS  Google Scholar 

  41. Jannini E.A., Ulisse S., D’Armiento M. Thyroid hormone and male gonadal function. Endocr. Rev. 1995, 16: 443–459.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, University of Maryland and Veterans Affairs Medical Center, Baltimore, Maryland, USA

    J. N. Rao

  2. Dept. of OCBS, University of Maryland Dental School, Rm. 4D-11, 666 West Baltimore Street, Baltimore, MD, 21201, USA

    J. Y. Liang, P. Chakraborti &  Pei Feng

Authors
  1. J. N. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Y. Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Chakraborti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pei Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pei Feng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rao, J.N., Liang, J.Y., Chakraborti, P. et al. Effect of thyroid hormone on the development and gene expression of hormone receptors in rat testes in vivo . J Endocrinol Invest 26, 435–443 (2003). https://doi.org/10.1007/BF03345199

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345199

Key-words

Search

Navigation