Endocrinology, Vol 132, 2417-2420, Copyright © 1993 by Endocrine Society

ARTICLES

Leydig cells increase their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism

MP Hardy, JD Kirby, RA Hess and PS Cooke
Population Council, New York, New York 10021.

Administration of the goitrogen, 6-propyl-2-thiouracil (PTU), to suckling rat pups from birth through day 24 postpartum as a 0.1% solution in the mother's drinking water increases adult testis size and sperm production by about 80% and 140%, respectively, without affecting peripheral testosterone levels. The objectives of this study were to determine whether adult Leydig cell numbers were altered in PTU-treated rats and whether the steroidogenic function of these cells was normal. The number of Leydig cells per testis at 180 days increased by 69% in PTU-treated compared to control rats, whereas the average Leydig cell volume declined by about 20%. Steroidogenic function assessed in isolated adult Leydig cells decreased after neonatal PTU treatment. LH- stimulated testosterone production was reduced by 55% in Leydig cells from treated rats, commensurate with a 50% decline in the number of hCG- binding sites in these cells. The difference in steroidogenic potential was even more striking after incubations with saturating concentrations of steroid substrate, 22(R)-hydroxycholesterol; Leydig cells from treated males produced 73% less testosterone than controls. Therefore, this decrease in testosterone production may be partially due to a reduction in the numbers of LH receptors, but also reflects the impaired steroidogenic potential of these cells. These results clearly show that the dramatic increase in adult Leydig cell number after neonatal PTU treatment is counterbalanced by a permanent decline in Leydig cell steroidogenic function, producing no net change in peripheral testosterone levels.

This article has been cited by other articles:

				K. De Gendt, N. Atanassova, K. A. L. Tan, L. R. de Franca, G. G. Parreira, C. McKinnell, R. M. Sharpe, P. T. K. Saunders, J. I. Mason, S. Hartung, et al. Development and Function of the Adult Generation of Leydig Cells in Mice with Sertoli Cell-Selective or Total Ablation of the Androgen Receptor Endocrinology, September 1, 2005; 146(9): 4117 - 4126. [Abstract] [Full Text] [PDF]

				F.-p. Zhang, T. Pakarainen, F. Zhu, M. Poutanen, and I. Huhtaniemi Molecular Characterization of Postnatal Development of Testicular Steroidogenesis in Luteinizing Hormone Receptor Knockout Mice Endocrinology, March 1, 2004; 145(3): 1453 - 1463. [Abstract] [Full Text] [PDF]

				N. St-Pierre, J. Dufresne, A. A. Rooney, and D. G. Cyr Neonatal Hypothyroidism Alters the Localization of Gap Junctional Protein Connexin 43 in the Testis and Messenger RNA Levels in the Epididymis of the Rat Biol Reprod, April 1, 2003; 68(4): 1232 - 1240. [Abstract] [Full Text] [PDF]

				Y.-C. Chiao, W.-L. Cho, and P. S. Wang Inhibition of Testosterone Production by Propylthiouracil in Rat Leydig Cells Biol Reprod, August 1, 2002; 67(2): 416 - 422. [Abstract] [Full Text] [PDF]

				S. L. P. Matta, D. A. R. Vilela, H. P. Godinho, and L. R. Franca The Goitrogen 6-n-Propyl-2-Thiouracil (PTU) Given during Testis Development Increases Sertoli and Germ Cell Numbers per Cyst in Fish: The Tilapia (Oreochromis niloticus) Model Endocrinology, March 1, 2002; 143(3): 970 - 978. [Abstract] [Full Text] [PDF]

				P. R. Manna, J. Kero, M. Tena-Sempere, P. Pakarinen, D. M. Stocco, and I. T. Huhtaniemi Assessment of Mechanisms of Thyroid Hormone Action in Mouse Leydig Cells: Regulation of the Steroidogenic Acute Regulatory Protein, Steroidogenesis, and Luteinizing Hormone Receptor Function Endocrinology, January 1, 2001; 142(1): 319 - 331. [Abstract] [Full Text] [PDF]

				H.B. Siril Ariyaratne, J. Ian Mason, and S.M.L. C. Mendis-Handagama Effects of Thyroid and Luteinizing Hormones on the Onset of Precursor Cell Differentiation into Leydig Progenitor Cells in the Prepubertal Rat Testis Biol Reprod, September 1, 2000; 63(3): 898 - 904. [Abstract] [Full Text]

				H.B. Siril Ariyaratne, S.M.L. Chamindrani Mendis-Handagama, D. Buchanan Hales, and J. Ian Mason Studies on the Onset of Leydig Precursor Cell Differentiation in the Prepubertal Rat Testis Biol Reprod, July 1, 2000; 63(1): 165 - 171. [Abstract] [Full Text]

				J. J. Buzzard, J. R. Morrison, M. K. O'Bryan, Q. Song, and N. G. Wreford Developmental Expression of Thyroid Hormone Receptors in the Rat Testis Biol Reprod, March 1, 2000; 62(3): 664 - 669. [Abstract] [Full Text]

				K. J. Teerds, D. G. de Rooij, F. H. de Jong, and L. H. van Haaster Development of the Adult-Type Leydig Cell Population in the Rat Is Affected by Neonatal Thyroid Hormone Levels Biol Reprod, August 1, 1998; 59(2): 344 - 350. [Abstract] [Full Text]

				S.M.L.C. Mendis-Handagama, H.B.S. Ariyaratne, K.R. Teunissen van Manen, and R.L. Haupt Differentiation of Adult Leydig Cells in the Neonatal Rat Testis Is Arrested by Hypothyroidism Biol Reprod, August 1, 1998; 59(2): 351 - 357. [Abstract] [Full Text]

				A S Faqi, P R Dalsenter, H-J Merker, and I Chahoud Effects on developmental landmarks and reproductive capability of 3,3',4,4'-Tetrachlorobiphenyl and 3,3',4,4',5- Pentacholorobiphenyl in offspring of rats exposed during pregnancy Human and Experimental Toxicology, July 1, 1998; 17(7): 365 - 372. [Abstract] [PDF]

				S. Ulisse, N. Rucci, D. Piersanti, E. Carosa, F. M. Graziano, A. Pavan, P. Ceddia, M. Arizzi, P. Muzi, L. Cironi, et al. Regulation by Thyroid Hormone of the Expression of Basement Membrane Components in Rat Prepubertal Sertoli Cells Endocrinology, February 1, 1998; 139(2): 741 - 747. [Abstract] [Full Text] [PDF]

				D. Nalbant, S. C. Williams, D. M. Stocco, and S. A. Khan Luteinizing Hormone-Dependent Gene Regulation in Leydig Cells May Be Mediated by CCAAT/Enhancer-Binding Protein-{beta} Endocrinology, January 1, 1998; 139(1): 272 - 279. [Abstract] [Full Text] [PDF]

				J. D. Kirby, N. Arambepola, T. Porkka-Heiskanen, Y. K. Kirby, M. L. Rhoads, H. Nitta, A. E. Jetton, G. Iwamoto, G. L. Jackson, F. W. Turek, et al. Neonatal Hypothyroidism Permanently Alters Follicle-Stimulating Hormone and Luteinizing Hormone Production in the Male Rat Endocrinology, July 1, 1997; 138(7): 2713 - 2721. [Abstract] [Full Text] [PDF]