Ovarian sex steroid receptors and sex hormones in androgenized rats

Abstract

This study evaluated for the first time the effects of different doses of the anabolic steroid nandrolone decanoate (ND) on the expression of ovarian steroid receptors (AR, ER-α (ESR1) and ER-β (ESR2)) and related sex hormones after treatment and recovery periods in adult rats. The animals were injected subcutaneously with doses of ND (1.87, 3.75, 7.5 or 15 mg/kg b.w.) or mineral oil (control group) for 15 days, and the experimental groups were divided into three periods of evaluation: (a) ND treatment for 15 days, (b) ND treatment and recovery for a period of 30 days and (c) ND treatment and recovery for a period of 60 days. Estrous cycle was monitored daily. At the end of each period, rats were killed for collection of blood and ovaries. Persistent diestrus occurred in all rats during ND treatment and after 30-day recovery. The highest dose of ND was able to maintain all rats arrested at diestrus until 60-day recovery. The expression of steroid receptors varied in a dose- and period-dependent manner, having a more pronounced response with the dose of 15 mg ND/kg. ND treatment increased serum levels of testosterone, 17β-estradiol and dihydrotestosterone, especially at the highest doses of 7.5 and 15 mg ND/kg. No change was observed in the levels of follicle-stimulating hormone (FSH), whereas levels of the luteinizing hormone (LH) varied according to the dose and period. In conclusion, the ovarian sex steroid receptors and sex hormones were restored only at lower doses of ND and after a longer period of recovery.

Histopathological changes in androgenized ovaries are recovered by melatonin treatment

“…Treatment with different doses of ND is capable of promoting oestrous acyclicity . In this study, the persistence of the dioestrus stage occurred even in androgenized groups that were treated with MLT.…”

“…The administration of MLT recovered the ovarian weight in the androgenized animals, as there was follicular development and corpora lutea formation. It is documented that MLT decreases LH levels, whereas treatment with 7.5 mg ND/kg may increase the levels of this gonadotropin . In this study, treatment with MLT might have balanced the LH levels that were deregulated by the steroid, attenuating the damages on the ovarian function.…”

“…Although the role of MLT in the hypothalamic‐pituitary‐gonadal axis has not yet been fully elucidated, it is reported that the influence of MLT is greater on the ovulation process than on follicular growth . In this study, folliculogenesis was altered by ND and reversed by MLT, mainly in the MLT/ND group, whereas in the ND group, there was intense follicular atresia induced by an excess of circulating androgens (testosterone and DHT) …”

“…As previously reported, the damage to folliculogenesis in females receiving only ND was evidenced by intense follicular atresia, absence of mature antral follicles and decrease in the number of healthy follicles at different stages of maturation. There were presence of cystic structures mainly in the ND group and occasionally in the ND/MLT group, resulting from deregulation in hormonal balance and ovulation failure . However, mature healthy follicles were identified, but in the ND/MLT group, the more developed follicles were less frequent than those observed in the control, MLT and MLT/ND groups.…”

“…Simão et al reported that treatment with 7.5 mg ND/kg induced LH hypersecretion followed by an increase in testosterone and dihydrotestosterone levels, while FSH remained unchanged. In addition, oestrogen levels increased due to the interference of the drug in the synthesis of estradiol, mediated by the aromatase enzyme, whose concentrations were higher in the androgenized groups.…”