With the identification of the PAQR membrane receptors for progesterone the rapid effects of this hormone, not dependent on gene transcription, can be explained [6]. The response of steroid membrane receptors can be rapid, as in the case of sperm hypermotility, or can occur over a prolonged period of time as in the case of oocyte maturation in fish [17]
and amphibians [18, 19]. Class III are the hemolysin III-related receptors that have the deepest evolutionary roots but whose agonists are not known, these are PAQR 10 and PAQR 11 [20] and the bacterial hemolysin III large class of proteins, expressed in many bacterial species [7]. The latter have been shown to induce cytolysis of eukaryotic cells by pore formation [21]. In Saccharomyces cerevisiae, the selleck chemical Izh genes Inhibitor Library encode membrane proteins that also belong to the ubiquitous protein family that includes hemolysin III and vertebrate membrane
PAQR homologues. The Izh family (implicated in zinc homeostasis) consists of 4 different proteins: Izh1, Izh2, Izh3 and Izh4. All but the Izh1 have the 7 transmembrane domains of the PAQRs [22]. The agonist for Izh2 has been identified as osmotin, a plant defense protein that is a homologue of adiponectin [23]. Yeast mutants of the Izh proteins exhibit defects in zinc tolerance. Izh proteins have been reported to be regulated Oxalosuccinic acid by exogenous fatty acids, suggesting a role in lipid metabolism [24]. The effects of Izh proteins on zinc homeostasis have been related either directly or indirectly to their effects on lipid metabolism [24]. The effects of steroid hormones in the development of the parasitic forms of pathogenic dimorphic fungi, drug resistance and susceptibility to infection, makes the identification of specific steroid receptors and steroid binding proteins of outmost importance in the treatment of fungal infections [reviewed in [25]. In Paracoccidioides brasiliensis the susceptibility to infection was observed to be dependent on gender,
men being more susceptible than women, while in the case of Coccidioides immitis, pregnancy increases the risk of developing the disease [26]. In both of these cases, hormones were suggested as responsible for these differences. On the other hand, in vitro studies of the phase transition from mycelium to yeast in P. brasiliensis showed that the transition to the yeast form was inhibited in the presence of estrogen [25]. In Candida albicans, steroids were found to alter the response to antifungal drugs [25]. Nevertheless, the identification of progesterone membrane receptors in fungi has been elusive. As mentioned above, specific receptors for steroid hormones in pathogenic fungi have not been thoroughly studied and identified.