Abstract
The present study aims to investigate the effects and mechanisms of sarsasapogenin resistance to precocious puberty. Female Sprague Dawley rats were divided into a normal (N) group, model (M) group, leuprolide (L) group, and sarsasapogenin (Sar) group. Rats at 5 days of age were given a single subcutaneous injection of 300 micrograms of danazol to establish the precocious puberty model. After 10 days of modeling, drug intervention was started. The development of the uterus and ovary was observed by hematoxylin and eosin (HE) staining. The levels of the serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) were determined by radioimmunoassay. Also, the expressions of the hypothalamic gonadotropin releasing hormone (GnRH), Kiss-1, G protein-coupled receptor 54 (GPR54), and pituitary gonadotropin releasing hormone receptor (GnRH-R) were detected by RT-PCR. The results showed that compared with the model group, sarsasapogenin could significantly delay the opening time of vaginal, decreased uterine and ovarian coefficients, and reduced uterine wall thickness. Moreover, it can significantly downregulate the levels of serum hormones and reduce the expression of GnRH, GnRH-R, and kiss-1. In summary, our results indicate that sarsasapogenin can regulate the HPG axis through the kiss-1/GPR54 system for therapeutic precocious puberty.
Highlights
Precocious puberty, a growth and development disorder, is caused by the premature activation of gonadotropin releasing hormone (GnRH) neurons [1]
A Danish study showed that the prevalence of precocious puberty in girls was 0.2%, that of boys was less than 0.05%, and the prevalence of girls was much higher than boys [3]
After 10 days of modeling, the L group was subcutaneously injected with leuprolide (Livzon Pharmaceutical Co., Ltd., Shanghai, China) at a dose of 100 μg/kg, and the Sar group was gavaged with a dose of 4 mg/kg (Yuanye Bio-Technology Co., Ltd., Shanghai, China). e N and M groups were given the same amount of saline
Summary
Precocious puberty, a growth and development disorder, is caused by the premature activation of GnRH neurons [1]. Leuprolide plays a significant role in the treatment of precocious puberty, it has been found that it is easy to cause vaginal bleeding when used for the first time, with an incidence of 16%–60% [12] It can increase the incidence of polycystic ovary syndrome [13]. The traditional Chinese medicine Zicao (Radix Lithospermi), based on its antifertility effect, has been found to reduce serum FSH, LH, and estradiol (E2) in rats, delay the opening time of the vagina, and play a role in therapeutic precocity by inhibiting the HPG axis. It had been reported that women with danazol administration did not influence serum levels of estradiol, but resulted in an increase in LH pulse amplitude in women with endometriosis [26]
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