Steroid binding proteins have been described for various yeasts [42]. Many studies have predicted the existence of a progesterone receptor in the membrane of filamentous fungi such as Rhizopus nigricans[27–30] but the molecular basis of steroid signalling in fungi remains unresolved [43, 44]. Progesterone has been Screening Library reported to bind to enriched plasma membrane fractions of R. nigricans with high affinity and this hormone
has been reported to induce an activation of G proteins that decreases in the presence of cholera toxin [29]. Nevertheless, to date no progesterone receptor has been directly identified in this or any other fungi. This work identified STA-9090 a membrane progesterone receptor for the first time in fungi. Progesterone was identified as the ligand corresponding to SsPAQR1 using the yeast-based assay [23, 45]. This assay was used previously to identify the ligands of human PAQRs
heterologously Belinostat manufacturer expressed in S. cerevisae[46]. This assay is specific for PAQRs and was intended for the study of these receptors without the intervention of other possible progesterone binding protein. Using this assay, SsPAQR1 was expressed in S. cerevisiae and progesterone was identified as the ligand for SsPAQR1. Yeasts carrying the empty expression vector showed that progesterone did not affect FET3, showing that the effect was not due to a nonspecific effect of progestrone on S. cerevisiae. Progesterone responsiveness was only observed if SsPAQR1 was being expressed. These results put an end to the uncertainty regarding the presence of a membrane progesterone receptor in fungi. Ribose-5-phosphate isomerase However, the question as to why fungi
have a steroid hormone receptor remains unanswered. The effects of progesterone and other steroids on fungi have not been fully documented. In Candida albicans the response to steroid hormones leads to the activation of transcription of genes encoding the ATP-binding cassette of drug efflux pumps [47]. In S. cerevisiae exposure to progesterone results in the up-regulation of stress response genes such as those involved in transport, oxidative stress response, growth, cell division and cell wall biogenesis, among other [43]. In the filamentous fungi, most of the information regarding progesterone and fungi is related to bioconversion of the different steroid metabolites by fungi. Recently, a progesterone-hydroxylating enzyme system was studied and found to be dependent on the G protein beta subunit and cAMP in Fusarium oxysporum[48]. The authors proposed that progesterone is toxic to this fungus and that by the induction of the enzymes involved in the hydroxylation of progesterone, the fungus is able to reduce the toxicity associated with the hormone. This transformation results in a more soluble compound that can be excreted to the medium. The toxicity of progesterone results in an inhibition of growth in R. nigricans[49].
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