Chronic hypothyroidism only marginally affects adult-type Leydig cell regeneration after EDS administration.
Chronic prenatally induced dietary hypothyroidism delays adult-type Leydig cell development, but does not block this process. Using a chemical model to induce hypothyroidism, it was suggested that development of a new population of Leydig cells was completely inhibited following the addition of the cytotoxic compound ethane-1,2-dimethyl sulphonate (EDS). In this study, we used a dietary approach to induce hypothyroidism and reinvestigated the regeneration of the Leydig cell population following EDS administration. Eighty-four day old euthyroid and chronically hypothyroid rats received an injection of EDS and were killed directly before or at regular intervals up to 77 days after EDS. In some control and hypothyroid animals, the first progenitor-type Leydig cells were observed at day 12 after EDS. At day 16, Leydig cell progenitors were present in all rats. The percentage of proliferating Leydig cells peaked in the euthyroid animals at day 21 after EDS. In the hypothyroid testis such a peak was not observed, although the percentage of proliferating regenerating Leydig cells was significantly higher from days 35 to 56 compared with the controls. This suggested that the wave of Leydig cell proliferation was delayed in the hypothyroid animals as compared with the euthyroid controls. On the day of EDS injection, the Leydig/Sertoli cell ratio was 37% lower in the hypothyroid rats compared with the controls. The Leydig/Sertoli cell ratio remained lower in the EDS-treated hypothyroid animals compared with the controls at all time points investigated. At day 77 after EDS, the Leydig cell population had returned to its pre-treatment size in both groups. Plasma testosterone production was reduced to below detectable levels immediately after EDS injection, and started to increase again on day 16, reaching pre-treatment values on day 21 in both groups. Taken together, severely reduced thyroid hormone levels did not block the regeneration of the adult-type Leydig cell population following EDS, as has been suggested previously.
Rijntjes
Eddy
E
Department of Animal Sciences, Human & Animal Physiology Group, Wageningen University, Wageningen, The Netherlands.
van Kesteren-Buiting
Anita
A
Keijer
Jaap
J
Teerds
Katja J
KJ
D000476:Alkanesulfonates; D000818:Animals; D004980:Ethane; D007037:Hypothyroidism; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D013737:Testis / Q000187:drug effects; D013963:Thyroid Hormones
D000476:Alkanesulfonates; D013963:Thyroid Hormones; D004980:Ethane