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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/E305    most recent 90750.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rijntjes, E. Articles by Teerds, K. J. Search for Related Content PubMed PubMed Citation Articles by Rijntjes, E. Articles by Teerds, K. J.

Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development

¹Department of Animal Sciences, Human and Animal Physiology Group, Wageningen University, Wageningen, The Netherlands; and ²Faculty of Sciences, School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, Australia

Submitted 5 September 2008 ; accepted in final form 25 November 2008

Transient hypothyroidism induced by propyl-2-thiouracyl blocks postpartum Leydig cell development. In the present study, the effects of chronic hypothyroidism on the formation of this adult-type Leydig cell population were investigated, using a more physiological approach. Before mating, dams were put on a diet consisting of an iodide-poor feed supplemented with a low dose of perchlorate and, with their offspring, were kept on this diet until death. In the pups at day 12 postpartum, plasma thyroid-stimulating hormone levels were increased by 20-fold, whereas thyroxine and free tri-iodothyronine levels were severely depressed, confirming a hypothyroid condition. Adult-type progenitor Leydig cell formation and proliferation were reduced by 40–60% on days 16 and 28 postpartum. This was followed by increased Leydig cell proliferation at later ages, suggesting a possible slower developmental onset of the adult-type Leydig cell population under hypothyroid conditions. Testosterone levels were increased 2- to 10-fold in the hypothyroid animals between days 21 and 42 postpartum compared with the age-matched controls. Combined with the decreased presence of 5-reductase, this implicates a lower production capacity of 5-reduced androgens. In 84-day-old rats, after correction for body weight-to-testis weight ratio, plasma insulin-like factor-3 levels were 35% lower in the hypothyroid animals, suggestive of a reduced Leydig cell population. This is confirmed by a 37% reduction in the Sertoli cell-to-Leydig cell ratio in hypothyroid rats. In conclusion, we show that dietary-induced hypothyroidism delays but, unlike propyl-2-thiouracyl, does not block the development of the adult-type Leydig cell population.

thyroxine; testosterone; insulin-like factor-3; Leydig cell proliferation