Transient Neonatal-Onset Hypothyroidism Boosts Estradiol Synthesis in the Testis of Adult Wistar Rat

Abstract

Transient neonatal hypothyroidism is known to boost Sertoli cell (SC), Leydig cell (LC) and germ cell (GC) number at adult age. Existing reports attribute decreased steroidogenic potential of LCs to unaltered/decreased serum testosterone in such rats, despite a boost in the cell number. However, these studies have ignored the status of estradiol in such conditions. In this present study, we tested the hypothesis neonatal-onset hypothyroidism may lead to a temporal shift in adult rat testicular steroidogenesis towards estradiol production. Hypothyroidism was induced in neonates by providing methimazole (MMI) in drinking water (0.05%) to lactating mothers and pups for a transient period from postnatal day 1 (PND 1) to PND 14 or from PND 1 to PND 29. After the experimental period, the pups were provided drinking water free of MMI and sacrificed on PND 91. Coeval rats without MMI exposure served as control. Radioimmunoassay revealed decreased serum titres of luteinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH) and prolactin (PRL); while serum testosterone remained unaltered, its level in testicular interstitial fluid (TIF) decreased. Between the two major metabolites of testosterone, 5α-dihydrotestosterone (DHT) concentration decreased in serum and TIF, whereas estradiol recorded a significant increase in both. Transient neonatal-onset hypothyroidism decreased 3β-hydroxy steroid dehydrogenase (3β-HSD) in LCs but augmented 17β-HSD activity. Radio-receptor assay revealed decreased concentration of LHR and ER in LCs of hypothyroid groups, whereas AR and PRLR increased. While aromatase activity decreased in LCs, it increased along with FSHR in SCs, when compared to control rats. The changes in LHR and FSHR levels and aromatase were consistent with the expression level of the respective genes. The present study supports the proposed hypothesis and suggests that transient neonatal-onset hypothyroidism-induced boost in estradiol in adult rat testis may be due to augmented expression and activity of aromatase, and FSHR content in SCs of these rats.