Consequences of hypothyroidism and thyrotoxicosis triggered in adulthood on male gonadal function: gene expression of molecular markers and proteomic profile in tissues of the hypothalamic-pituitary-gonadal axis

Abstract

Thyrotoxicosis and hypothyroidism produce adverse effects on the reproductive function of male men and animals. Hypothyroidism is associated with hypogonadism, reduction in the testosterone serum concentrations e other androgens, and sperm morphological abnormalities and thyrotoxicosis induces alterations in sperm motility. However, the mechanisms by which the thyroid hormones interfere with the reproductive axis are still unknown. Recently, our group reported that rats that developed hypothyroidism in adulthood presented increase in the expression of luteinizing hormone, occurring posttranscriptional regulation of this transcript by reducing both the poly(A) tail length and association to polysomes; decreased serum testosterone concentration, despite the high serum LH; and reduction of the seminiferous epithelium. In this manner, the objective of this study is to advance the knowledge of the molecular mechanisms that affect the hypothalamic-pituitary-gonadal (HPG) axis in hypothyroidism and thyrotoxicosis. For this, we will use male Wistar rats that developed hypothyroidism or thyrotoxicosis in adulthood as experimental model and the following parameters will be evaluated: acrosome and plasma membrane integrities, mitochondrial activity and sperm morphology; sperm production; quantification of mRNAs of the genes related to the regulation of the HPG axis in the hypothalamus (GnRH, AR, ESR1, ESR2), in the pituitary (GnRHR, LH, FSH, AR, ESR1, ESR2), in the testis and epididymis (LHR, FSHR, AR, ESR1, ESR2, GPER, TR); proteomic analysis in the same tissues; and dosage of serum concentrations of testosterone, estradiol, LH, FSH, T3 and TSH. (AU)