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

Abstract

Rijntjes E, Swarts HJ, Anand-Ivell R, Teerds KJ. Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development. Am J Physiol Endocrinol Metab 296: E305-E314, 2009. First published November 25, 2008 doi:10.1152/ajpendo.90750.2008.-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.

The syndrome of central hypothyroidism and macroorchidism: IGSF1 controls TRHR and FSHB expression by differential modulation of pituitary TGFβ and Activin pathways

“…The mechanism was the cross-reactive stimulation of testicular FSHR by chronic and extremely high elevations of TSH in such boys from birth55. In rat models, hypothyroidism induces macroorchidism as a consequence of increased Sertoli cell numbers with reduced Leydig cell numbers at puberty565758596061. However, two essential differences exist between the hypothyroid conditions mentioned and our patient.…”

Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats

“…The animals had free access to food and tap water and were provided with cage enrichment in the form of a 10 cm sisal rope. Two weeks after arrival the female rats of the experimental group ( n  = 9) were put on an iodide-poor diet based on AIN 1993 requirements (Research Diet Services, Wijk bij Duurstede, the Netherlands) [18] supplemented with 0.75% sodium perchlorate in the drinking water to deplete endogenous iodie store [19, 20]. This treatment leads already within two weeks time to a 16-fold increase in plasma TSH concentrations [17].…”

Nuclear Receptors in Leydig Cell Gene Expression and Function1

“…More recently, dietary-induced prenatal hypothyroidism was found to delay differentiation of the ALC population without affecting the fetal population [18]. Thyroid hormone acts through two distinct thyroid hormone receptors: NR1A1 (TRa) and NR1A2 (TRb).…”