TNF-alpha, recombinant rat protein br Dihydrotestosterone in
Dihydrotestosterone in adult fish and frogs
New perspectives and next directions Similar to other androgens, DHT can modulate reproductive endpoints in both fish and amphibians. However, predicting the effects of DHT can be challenging, as reproductive homeostasis is dependent upon the balance between estrogenic and androgenic hormones in addition to many other signaling molecules. We have summarized the documented effects of DHT in fish and frogs (Fig. 4) as an initial framework for uncovering the molecular mechanisms of action of DHT in aquatic vertebrates. In male fish, DHT treatments can both stimulate and inhibit androgen production, while in female fish, DHT has been shown to increase Vtg synthesis in vitro from hepatocytes, increase E2 production from the ovary, and can inhibit plasma Vtg with in vivo exposures. However, there is currently a lack of understanding regarding the significance of the DHT pathway in teleost fishes and TNF-alpha, recombinant rat protein in the context of reproduction and even less data for a role in other physiological processes. This is a significant knowledge gap as androgens are well documented to affect multiple biological pathways outside the reproductive axis. Martyniuk and Denslow (2012) summarized molecular-based studies investigating androgens in fish and point out there are molecular responses that appear to be common to androgens, as identified using transcriptomics and proteomics approaches. These processes include apoptosis, lipid regulation, immune function, xenobiotic pathways, and cell differentiation. These biological processes are also likely to be under the influence of DHT. We propose, that to move our understanding of the roles of DHT forward, studies are needed that (1) address how DHT is synthesized within tissue of fish and amphibians; (2) determine the biological responses to DHT, and its interactions with other signaling pathways; and (3) investigate how DHT synthesis varies with reproductive stage. All three 5-alpha-reductase isoforms are present in the adult FHM ovary and testis, and it appears as though there is sex-specific expression of the three isoforms; however the relative activity of each in the teleostean gonad is not known. This topic can be addressed by studies that explore the seasonal expression patterns in srd5a expression as well as their seasonal activity. Moreover, data on the role of 5-beta-reduced steroids and the expression patterns of srd5b are also scarce, although it appears as though the 5 beta-reduced steroids are important for spermiation in male catfish (Schoonen et al., 1987) and that srd5b is expressed in male and female frog livers and brains (Langlois et al., 2011, Duarte-Guterman and Trudeau, 2009). This alternate DHT metabolic pathway may also be required for normal development and reproduction. A final point to make is that distinguishing the biological effects of DHT from its metabolic precursor testosterone will be challenging. Pharmaceutical agents such as 5α-reductase inhibitors (e.g., dutasteride and finasteride) will prove useful for the elucidation of the molecular responses to DHT and these types of studies are lacking in fish. Conversely, there is a growing body literature for amphibians for 5-alpha-reductase inhibitors; however studies are lacking on direct effects of DHT in frogs. Moreover, metabolites of DHT are of potential interest. For example, 5 alpha-androstane-3 beta, 17 beta-diol has been shown to bind ERs in mammals (Kuiper et al., 1997). This complicates the characterization of androgenic and estrogenic signaling pathways and well-designed experiments are required in order to dissect the direct effects of DHT. Sex steroid hormones have multiple mechanisms of action that are dependent upon the activity of the biosynthetic pathway in an individual at a given time. Currently, characterizing the entire complement of steroid hormones and growth factors within a tissue is not possible, but perhaps a viable strategy is to utilize a meta-analysis approach to uncover commonly regulated pathways to various androgens. This will improve our understanding ultimately of how steroids regulate gonadal function and reproductive processes in aquatic vertebrates.