Luteinizing hormone regulates seasonal steroidogenesis locally in the prostate of muskrat (Ondatra zibethicus).

The prostate is one of the important androgen-dependent organs in the male reproductive system. Although its ability for local steroid hormone synthesis is recognized, the regulatory mechanisms, particularly the role of hormones and the seasonal steroidogenesis expression within the tissue, remain unclear. This study investigated the phenomenon in the seasonal breeder muskrat (Ondatra zibethicus) by comparing breeding (B) and non-breeding (NB) season prostates through histology, immunohistochemistry (IHC), RT-qPCR, and hormone assays. Anatomy shows that the prostate is markedly enlarged during the breeding season. Immunohistochemistry revealed a marked cellular compartmentalization: luteinizing hormone receptor (LHR), steroidogenic acute regulatory protein (StAR), and Steroid 5-alpha-reductase 2 (SRD5A2) were predominant in epithelial cells, whereas cytochrome P450 family 11 subfamily A member 1 (P450scc) and steroid 17 alpha-hydroxylase (P450c17) were primarily localized to stromal cells. The gene expression of steroidogenesis pathway was coordinately upregulated in the breeding season, and largely downregulated in the non-breeding season, which was further validated at the protein level by Western blot analysis showing significantly higher expression of LHR, P450scc, SRD5A2, and androgen receptor (AR) in the breeding season compared to the non-breeding season. The prostate in the breeding season was contained higher levels of intra-tissue testosterone (T) and dihydrotestosterone (DHT). To investigate the underlying mechanism, we performed in vitro experiments using primary cultured muskrat prostate cells. Furthermore, in vitro experiments demonstrated that human chorionic gonadotropin (HCG) treatment promoted the expression of LHR and steroidogenic enzymes, as well as elevated the secretion of T and DHT into the culture media. This induction was inhibited by the Protein Kinase A (PKA) inhibitor H89, which also abolished the HCG-induced increase in T and DHT secretion. H89 pre-treatment abolished the HCG-induced upregulation, confirming the presence of the LH-PKA pathway regulating steroidogenesis in the prostate. Taken together, our results reveal that LH-mediated activation of local steroidogenesis may regulate the seasonal growth of prostates in male muskrats.