Developmental Hormonal Profiles in rdw Rats with Congenital Hypothyroidism Accompanying Increased Testicular Size and Infertility in Adulthood

Abstract

Abstract. Congenital hypothyroid mutant male rdw rats have enlarged testes in adulthood with dwarfism accompanied by infertility. To explain how rdw rats acquire enlarged testes in adulthood, we compared age-matched normal (N) rats at various developmental stages for blood levels of hormones, thyroxine (T4), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T), and investigated whether T4 therapy (rdw+T4) from 3 weeks of age (w) until adulthood could induce recovery of fertility in rdw rats, as well as how rdw+T4 affected hormonal patterns. Testes weights of rdw rats were higher than those of N rats at 19 w in adulthood though it was low during development. Serum T4 values in rdw rats were markedly lower than those in N rats but steadily increased up to 19 w. The serum FSH values in rdw rats were lower than those in N rats at all ages, and neither serum LH nor T value was significantly different at any age. The testes weight of rdw+T4 rats was significantly higher than that of N rats at 13 w with recovered growth, and was higher than that of rdw rats at 19 w. When they were mated with proestrous females after 16 w, all females became pregnant and gave birth to a normal number of pups. The T4 and FSH values of rdw+T4 rats were significantly higher than those in rdw rats, but similar to those in N rats in adulthood. The results suggest that even low levels of circulating thyroid hormone (TH) in rdw rats stimulate the development of their testes, probably through Sertoli cells, resulting in the enlarged adult testes without fertility, and that a sufficient circulating TH level from the immature stage plays a pivotal role in restoring mating activity, probably through FSH-mediated action towards adulthood.

Effects of male sexual maturity of reproductive endpoints relevant to DART studies in Wistar Hannover rats

“…In Sprague Dawley rats, serum testosterone level began to increase at about 3 weeks of age and continue to rise until adult levels at about 10 weeks of age (Korenbrot et al, 1977;Chan et al, 1981). On the other hand, serum testosterone increased from 7 weeks of age and was maximal at 13 weeks of age in Wistar rats (Umezu et al, 2004). Together with these reports, the current study suggests that there might be an age-related difference in testosterone production between the two strains and this difference would affect the timing of sperm maturation.…”

Rescue from Dwarfism by Thyroid Function Compensation in rdw Rats

“…In the rdw rat, the thyroxine (T 4 ) levels in serum are drastically decreased [19,21,23], but the thyroid-stimu-…”

“…Thus, we concluded that the rdw rat has primary hypothyroidism. Umezu et al have recently shown that male rdw rats show recovery of body weight with fertility in response to T 4 supplementary therapy from 3 weeks of age until adulthood [24].…”

“…Subsequently, it was revealed that the expressions of mRNA (Received 28 February 2005 / Accepted 1 September 2005 Address corresponding: S. Furudate, Department of Laboratory Animal Science, Japan of growth hormone (GH) and prolactin (PRL) in the rdw rat are drastically decreased [18,21]. In addition, the GH and PRL proteins in the rdw rat are decreased to a level 1/30 to 1/100 of those of a normal rat [17,18].In the rdw rat, the thyroxine (T 4 ) levels in serum are drastically decreased [19,21,23], but the thyroid-stimu- …”

“…lating hormone (TSH) levels are elevated [19,23], implicating dysfunction of the thyroid gland. In addition, two-dimensional gel electrophoresis studies conducted on various tissues of the rdw rat have revealed that the rdw thyroid glands have a very serious abnormality in protein content [17].…”