Sexual dimorphism in thyroid function and type 1 iodothyronine deiodinase activity in pre-pubertal and adult rats

Abstract

Iodothyronine deiodinase activities are regulated by sex steroids; however, the mechanisms underlying the reported sexual dimorphism are poorly defined. In the present report, we aimed to investigate whether type 1 deiodinase (D1) sexual dimorphism exists early in sexual development by studying pre-pubertal male (Pm) and female (Pf) rats, as well as adult controls (C) and gonadectomized male and females rats. Adult male Wistar rats were studied 21 days after orchiectomy (Tex), and adult females were studied 21 days after ovariectomy (Ovx), and after estradiol benzoate (Eb) replacement. Serum total triiodothyronine (T3) was higher in pre-pubertal (P) rats than in the matching adults, with no difference between genders, although in adult males T3 was significantly lower than in females. There were no sex or age differences in serum total T4. Serum TSH in pre-pubertal (P) rats was within the adult female range, and both were significantly lower than in adult males. D1 activity in liver was greater in Pm than in Pf. In adult females, liver D1 activity was lower, while in adult males it was higher than in P rats. The same pattern of D1 activity was found in kidney. In thyroid and pituitary, D1 activity was similar in Pm, Pf, and adult females, which were all significantly lower than in the adult male. There were no differences in serum T3 and T4 between C and Tex males, but serum TSH was significantly decreased in Tex rats. Hepatic and renal D1 activities were lower in Tex than in C, but no changes were detected in thyroid and pituitary. In Ovx females, T3 was significantly lower than in the C group. Serum T4 was significantly decreased by estradiol replacement therapy in Ovx rats, in both doses used, whereas TSH was unchanged. Eb replacement increased liver and thyroid D1 activity, but in the kidney, only the highest estradiol dose promoted a significant D1 increase. In conclusion, in males, hepatic and renal D1 activity appears to be significantly influenced by gonadal hormones, in contrast to females, in which only exogenous Eb treatment stimulated D1 activity. The comparison between pre-pubertal and adult rats suggests that serum T3 is not the main regulator of D1 activity, and other factors, besides T3 and gonadal hormones, can modulate D1 activity during murine maturation.

Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity

“…High levels of DIO1 activity were found in these peripheral organs, both in rats and in humans (Visser 1996). Under our experimental conditions, a decrease in liver Dio1 expression, accompanied by a corresponding decrease in enzyme activity, was detected in Orx middle-aged rats, in line with other authors who demonstrated the same for Orx prepubertal and adult rats (Miyashita et al 1995, Lisbôa et al 2001, Marassi et al 2007). …”

“…Therefore, it was speculated that a difference in serum TSH between males and females is, at least, partly due to change in DIO1 enzyme activity. It is well known that castration of young adult males significantly reduces circulating levels of TSH (Christianson et al 1981, Bagchi et al 1984, Borges et al 1998, Marassi et al 2007). However, in line with the results of this study, those who examined the effects of castration in older males demonstrated no effect on TSH level in circulation (Bagchi et al 1984, Chen 1984.…”

“…However, elderly men with thyroid carcinomas have much worse prognosis than women (Morganti et al 2005). In animal models, rats in particular, sexual dimorphism is more clearly evident than in humans: young adult males have higher serum TSH levels than females (Chen 1984, Banu et al 2001, Marassi et al 2007. In addition to effects on hypothalamic-pituitary hormone regulation (Donda et al 1990, Köhrle et al 1995, Schomburg & Bauer 1997, both testosterone and estrogen may differently affect thyroid homeostasis in vivo by affecting thyroid follicular epithelium (Pelletier & El-Alfy 2000, Banu et al 2002, level of TH carrier proteins in circulation (Bisschop et al 2006), and/or DIO enzyme activities in peripheral organs (Köhrle et al 1995, Lisbôa et al 2001.…”

Regulation of TRH neurons and energy homeostasis-related signals under stress

“…Estrogen modulates the expression of several orexigenic and anorexigenic peptides and hormones (Brown & Clegg 2010). Male rats are more sensitive to insulin and females to leptin; compared with males, females adapt more efficiently to energy deficits, are more susceptible to HPT inhibition by food restriction, have lower pituitary expression of TSHb and serum TSH associated with higher levels of T 3 , and reduced hepatic activity of D1 under basal conditions (Cizza et al 1996, van Haasteren et al 1996, Valle et al 2005, Marassi et al 2007. Estrogen stimulates thyroid function, increasing iodide uptake and thyroid peroxidase activity which would increase TH biosynthesis (Lima et al 2006).…”

Abuso de esteróides anabolizantes e seu impacto sobre a função tireóidea

“…(1997) não detectaram alterações no T 3 e T 4 séricos totais em ratas castradas tratadas ou não com estrogênio, porém Marassi e cols. (2007) evidenciaram diminuição de T 4 total em ratas castradas tratadas com estrogênio nas doses fisiológicas e suprafisiológicas, além de um aumento na atividade da D1 hepática e tireóidea nos dois grupos acima e hipofisária apenas no grupo tratado com dose fisiológica (38,40).…”