A unique system has been developed for studying the factors which control the establishment of the adult number of Sertoli cells and the growth and sperm production of the testis. With this method, testis size and sperm production in adult rats can be increased 80% and 140%, respectively, by a short neonatal treatment with the reversible goitrogen 6-propyl-2-thiouracil (PTU). Furthermore, Sertoli cell numbers are increased by 170% in PTU-treated rats. The mechanisms by which PTU treatment increases testis growth and sperm production are unknown, but increased Sertoli cells proliferation appears to be the critical event in the development of this effect. The studies in this proposal will use both in vitro and in vivo approaches to determine the mechanism by which PTU treatment increases Sertoli cell numbers, and will test two basic hypotheses. First, that the lack of thyroid hormones in PTU-treated rats delays the maturation of Sertoli cells, allowing them to remain in a juvenile, proliferative stage longer during early postnatal development. Second, that another factor(s) (e.g., increased TSH and increased Sertoli cell responsiveness to FSH) stimulates Sertoli cell mitosis during this extended postnatal proliferative period, resulting in the increased adult Sertoli cell numbers and secondarily, the observed increases in testis weight and sperm production. The results of these studies should specifically increase our understanding of the role of thyroid hormones in Sertoli cell proliferation and further our knowledge of the factors which regulate early Sertoli cell proliferation and the establishment of the ultimate adult numbers of these cells. This study will determine: 1) Whether Sertoli cell proliferation is increased in magnitude and/or prolonged by PTU treatment; 2) if TSH can be mitogenic for Sertoli cells from treated and/or control rats in vitro; 3) whether PTU treatment increases the FSH responsiveness of Sertoli cells from treated rats; 4) if PTU treatment alters the age-related decrease in mitogenic responsiveness that normally occurs during the neonatal period; 5) whether thyroid hormones control the age-related decrease in mitogenic responsiveness of neonatal Sertoli cells; 6) possible differences in FSH receptor expression in control and treated Sertoli cells; 7) possible differences in thyroid hormone receptor expression in control and treated Sertoli cells; 8) the importance of Sertoli cell-germ cell interactions for the increased Sertoli cell proliferation seen in PTU-treated rats.

Project Start
1992-07-01
Project End
1997-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Veterinary Medicine
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Jansen, Heiko T; Kirby, John D; Cooke, Paul S et al. (2007) Impact of neonatal hypothyroidism on reproduction in the male hamster, Mesocricetus auratus. Physiol Behav 90:771-81
Arambepola, N K; Bunick, D; Cooke, P S (1998) Thyroid hormone and follicle-stimulating hormone regulate Mullerian-inhibiting substance messenger ribonucleic acid expression in cultured neonatal rat Sertoli cells. Endocrinology 139:4489-95
Arambepola, N K; Bunick, D; Cooke, P S (1998) Thyroid hormone effects on androgen receptor messenger RNA expression in rat Sertoli and peritubular cells. J Endocrinol 156:43-50
Cooke, P S; Buchanan, D L; Lubahn, D B et al. (1998) Mechanism of estrogen action: lessons from the estrogen receptor-alpha knockout mouse. Biol Reprod 59:470-5
Cunha, G R; Young, P; Hom, Y K et al. (1997) Elucidation of a role for stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants. J Mammary Gland Biol Neoplasia 2:393-402
Kirby, J D; Arambepola, N; Porkka-Heiskanen, T et al. (1997) Neonatal hypothyroidism permanently alters follicle-stimulating hormone and luteinizing hormone production in the male rat. Endocrinology 138:2713-21
Hess, R A; Gist, D H; Bunick, D et al. (1997) Estrogen receptor (alpha and beta) expression in the excurrent ducts of the adult male rat reproductive tract. J Androl 18:602-11
Cooke, P S; Buchanan, D L; Young, P et al. (1997) Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium. Proc Natl Acad Sci U S A 94:6535-40
Hardy, M P; Sharma, R S; Arambepola, N K et al. (1996) Increased proliferation of Leydig cells induced by neonatal hypothyroidism in the rat. J Androl 17:231-8
Cooke, P S; Zhao, Y D; Hansen, L G (1996) Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm production in the rat. Toxicol Appl Pharmacol 136:112-7

Showing the most recent 10 out of 16 publications