Differential regulation of anterior pituitary prodynorphin and gonadotropin-subunit gene expression by steroid hormones

Abstract

Prodynorphin is expressed by neurons of the hypothalamus and gonadotrophs of the anterior pituitary gland (AP) and plays a role in the negative feedback regulation of the reproductive neuroendocrine axis. The present study examined whether gonadal steroid hormones are capable of modulating pituitary prodynorphin expression in immature, female rats. Steroids were administered via subcutaneous Silastic implants and rats were killed at 29 days of age. Northern blot analysis was used to measure AP prodynorphin, luteinizing hormone-/gb (LH/gb), follicle-stimulating hormone-/gb (FSH/gb), and common α-subunit mRNA levels (normalized to 18S ribosomal RNA). Treatment groups ( n = 5–6) consisted of control (CNT; empty implants), estradiol (E 2; 4 days), E 2 + progesterone (E 2 + P 4; 8 days and 4 days, respectively), and dihydrotestosterone (DHT; 4 days). Pituitary prodynorphin mRNA was significantly suppressed in only the DHT-treated animals (26 ± 10% of CNT, p < 0.01). LH/gb mRNA was suppressed by all steroid treatments ( p < 0.01), FSH/gb was lower in only the E 2 group, and α-subunit was reduced in both the E 2 + P 4 and DHT groups ( p < 0.01). Serum LH was suppressed by all steroid treatments but FSH was reduced in only the E 2 and E 2 + P 4 groups ( p < 0.01). Treatment of prepubescent rats with continuous high levels of gonadal steroids is known to severely reduce endogenous hypothalamic gonadotropin releasing hormone (GnRH) release and this is supported by our observation of reduced gonadotropin-subunit gene expression. Since only DHT produced a significant reduction in AP prodynorphin expression, these data suggest that androgens can act directly on the pituitary to suppress prodynorphin expression.