Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development.
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 5alpha-reductase, this implicates a lower production capacity of 5alpha-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.
Rijntjes
Eddy
E
Dept. of Animal Sciences, Human & Animal Physiology Group, Wageningen Univ., Marijkeweg 40, 6709 PG Wageningen, The Netherlands.
Swarts
Hans J M
HJ
Anand-Ivell
Ravinder
R
Teerds
Katja J
KJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004032:Diet / Q000009:adverse effects*; D005260:Female; D048070:Fetal Nutrition Disorders / Q000503:physiopathology / Q000662:veterinary; D007037:Hypothyroidism / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology* / Q000662:veterinary; D007455:Iodine / Q000172:deficiency; D007985:Leydig Cells / Q000502:physiology*; D008297:Male; D009929:Organ Size; D010472:Perchlorates; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology* / Q000662:veterinary; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds; D013737:Testis / Q000473:pathology; D013997:Time Factors
D010472:Perchlorates; D017670:Sodium Compounds; D007455:Iodine; C031068:sodium perchlorate