Altered Expression of 3β‐HSD, CYP17 and 17β‐HSD in the Foetal Porcine Gonads in Response to Anti‐androgen Flutamide Exposure

Abstract

We investigated whether the limited access to androgens during late prenatal period alters expression of steroidogenic enzymes involved in androgen production: 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD), cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) or type 3 (17β-HSD3) in the foetal porcine gonads. Pregnant gilts were injected with anti-androgen flutamide (for seven days, 50 mg/day/kg bw) or corn oil (control) starting at 83 (GD90) or 101 (GD108) gestational day. To assess 3β-HSD, CYP17 and 17β-HSD1 or 17β-HSD3 expression, real-time PCR and immunohistochemistry were performed. In testes from flutamide-treated foetuses, increased 3β-HSD and CYP17 mRNA expression was observed in the GD90 group, while decreased 3β-HSD and 17β-HSD3 mRNA expression and increased CYP17 mRNA expression were found in the GD108 group. CYP17 and 17β-HSD3 were localized in Leydig cells. Following flutamide administration, the intensity of CYP17 immunostaining was higher in both treated groups, while 17β-HSD3 intensity was lower in the GD108 group. In ovaries from flutamide-treated foetuses in the GD90 group, mRNA level for 3β-HSD was elevated, but it was diminished for CYP17 and 17β-HSD1. In the GD108 group, flutamide treatment led to lower mRNA level for 3β-HSD but higher for CYP17. 3β-HSD was found in granulosa cells, while CYP17 was localized within egg nests and oocytes of forming follicles. Following flutamide treatment, the intensity of 3β-HSD and CYP17 immunostaining was higher in the GD90 and GD108 groups, respectively. Immunohistochemical staining for 3β-HSD was restricted to the ovary. Concluding, diminished androgen action in the porcine foetal gonads during late gestation induces changes in steroidogenic enzymes expression, which may led to changes in gonadal function. However, it seems that androgens exert diverse biological effects depending on the gestational period.

Assessment of testicular steroidogenic enzymes expression in experimental animal model following withdrawal of nandrolone decanoate

“…An interesting finding is the immunolocalization of HSD17B3 within seminiferous tubules, along with Leydig cells in the interstitial compartment. It is generally considered that testicular HSD17B3 is only localized in the Leydig cell of the testis [ 24 ], and a clear positive immuno-reactivity of HSD17B3 in rat Leydig cell has been observed in the current study. However, a strong immunolocalization of HSD17B3 in rat testis has also been detected in certain germ cell types, presumably spermatocytes, of certain spermatogenic stages.…”

“…However, the specific localization of HSD17B3 in germ cells has not yet been defined. The function of HSD17B3 is responsible for the conversion of androstenedione to testosterone [ 24 ]. Thus, the existence of HSD17B3 in specific germ cells could be relevant to the production of testosterone within the seminiferous tubule, which involves local regulation for maintaining the structure and function of cells residing within the germinal epithelium.…”

Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring

“…The present study also showed a notable decrease of 3β-HSD in adult F1 uterus and ovaries in both mRNA and protein levels, and this may explain the decrease of E 2 levels in F1 adult females. Reduction of 3β-HSD, an important steroidogenesis pathway enzyme, may affect the synthesis of E 2 , leading to abnormal changes in gonadal function [ 53 , 54 ].…”