Systemic distribution of progesterone receptor subtypes in human tissues.

Progesterone receptor (PR) is expressed in a wide variety of human tissues, including both reproductive and non-reproductive tissues. Upon binding to the PR, progesterone can display several non-reproductive functions, including neurosteroid activity in the central nervous system, inhibition of smooth muscle contractile activity in the gastrointestinal tract, and regulating the development and maturation of the lung. PR exists as two major isoforms, PRA and PRB. Differential expression of these PR isoforms reportedly contributes to different biological activities of the hormone. However, the distribution of the PR isoforms in human tissues has remained virtually unexplored. In this study, we immunolocalized PR expression in various human tissues using PR (1294) specific antibody, which is capable of detecting both PRA and PRB, and PRB (250H11) specific antibody. Tissues from the uterus, ovary, breast, placenta, prostate, testis, cerebrum, cerebellum, pituitary, spinal cord, esophagus, stomach, small intestine, colon, pancreas, liver, kidney, urinary bladder, lung, heart, aorta, thymus, adrenal gland, thyroid, spleen, skin, and bone were examined in four different age groups (fetal, pediatric, young, and old) in male and female subjects. PR and PRB were detected in the nuclei of cells in the female reproductive system, in both the nuclei and cytoplasm of pituitary gland and pancreatic acinar cells, and only in the cytoplasm of cells in the testis, stomach, small intestine, colon, liver, kidney, urinary bladder, lung, adrenal gland, and skin. Of particular interest, total PRB expression overlapped with that of total PR expression in most tissues but was negative in the female fetal reproductive system. The findings indicate that progesterone could affect diverse human organs differently than from reproductive organs. These findings provide new insights into the novel biological roles of progesterone in non-reproductive organs.

Receptor-based Surrogate Subtypes and Discrepancies with Breast Cancer Intrinsic Subtypes: Implications for Image Biomarker Development.

Purpose To determine the concordance and accuracy of imaging surrogates of immunohistochemical (IHC) markers and the molecular classification of breast cancer. Materials and Methods A total of 3050 patients from 17 public breast cancer data sets containing IHC marker receptor status (estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 [HER2]) and their molecular classification (basal-like, HER2-enriched, luminal A or B) were analyzed. Diagnostic accuracy and concordance as measured with the κ statistic were calculated between the IHC and molecular classifications. Simulations were performed to assess the relationship between accuracy of imaging-based IHC markers to predict molecular classification. A simulation was performed to examine effects of misclassification of molecular type on patient survival. Results Accuracies of intrinsic subtypes based on IHC subtype were 71.7% (luminal A), 53.7% (luminal B), 64.8% (HER2-enriched), and 81.7% (basal-like). The κ agreement was fair (κ = 0.36) for luminal A and HER2-enriched subtypes, good (κ = 0.65) for the basal-like subtype, and poor (κ = 0.09) for the luminal B subtypes. Introduction of image misclassification by simulation lowered image-true subtype accuracies and κ values. Simulation analysis showed that misclassification caused survival differences between luminal A and basal-like subtypes to decrease. Conclusion There is poor concordance between triple-receptor status and intrinsic molecular subtype in breast cancer, arguing against their use in the design of prognostic genomic-based image biomarkers. © RSNA, 2018 Online supplemental material is available for this article.

Establishment of procedures for studying mPR-interacting agents and physiological roles of mPR.

More than 10years have passed since the discovery of membrane progestin receptors (mPRs). Although the identification of mPR genes in various organisms and mPR expression patterns have been described since then, the precise physiological roles of mPRs are still unclear, except their function as a receptor for maturation-inducing steroid in fish. The wide distribution of mPRs suggests variable actions for progestins through mPRs in the tissues. Information about the physiological roles of mPRs, such as roles in the progression of breast cancer and T-cell proliferation, has gradually accumulated recently. These results suggest that mPRs are possible targets for new pharmaceuticals. We established a cell line that was transformed with cDNAs for mPRα and a recombinant luciferase gene named GloSensor. The cells can be used for monitoring the effects of ligands on mPRα based on intracellular cyclic adenosine monophosphate (cAMP) levels. Studies using these cell lines indicated that the cAMP concentration is decreased by ligands for mPRα. The results provide support for previous results suggesting that mPRα is coupled to inhibitory G protein (Gi). We also established screening methods that make it possible to screen ligands for mPR. Recently, we succeeded in expressing and purifying recombinant mPR protein in the yeast Pichia pastoris. Relatively large amounts of mPR protein with hormonal binding activity can be purified by our method. The recombinant protein will be applicable to establishing a molecular probe to detect mPR-interacting agents. To obtain decisive evidence for the roles of mPRs, we are establishing strains of medaka fish that are deficient in mPRs. In medaka, four subtypes of mPR genes (α, ß, γ, and α2) have been identified. By reverse genetic screening, we have selected three to four strains in which a point mutation has been induced in the coding sequence of the mPR subtypes. However, homozygous mutants of each mPR gene showed no phenotype. The results suggested that mPR genes share redundancy. We are currently producing double and triple mutants of the mPR subtypes. The physiological roles of mPRs will be demonstrated using the mutant medaka strains.

Efficient prediction of progesterone receptor interactome using a support vector machine model.

Protein-protein interaction (PPI) is essential for almost all cellular processes and identification of PPI is a crucial task for biomedical researchers. So far, most computational studies of PPI are intended for pair-wise prediction. Theoretically, predicting protein partners for a single protein is likely a simpler problem. Given enough data for a particular protein, the results can be more accurate than general PPI predictors. In the present study, we assessed the potential of using the support vector machine (SVM) model with selected features centered on a particular protein for PPI prediction. As a proof-of-concept study, we applied this method to identify the interactome of progesterone receptor (PR), a protein which is essential for coordinating female reproduction in mammals by mediating the actions of ovarian progesterone. We achieved an accuracy of 91.9%, sensitivity of 92.8% and specificity of 91.2%. Our method is generally applicable to any other proteins and therefore may be of help in guiding biomedical experiments.

Progesterone receptor isoforms in the mammary gland of cats and dogs.

Progesterone exerts its effect by binding to specific progesterone receptors (PR) within the cell. In dogs and cats, no data are available on PR isoforms as found in other species. We therefore investigated the sequence of the PR gene and encoded protein in dogs and cats, the expression of PR isoforms in mammary tissue using Western blots and the presence of PR in mammary tissue using immunohistochemistry. Comparison of the amino acid sequence of the canine and feline PR with human PR revealed major differences in the PR-B-specific upstream segment (BUS). However, the essential activation function 3 (AF3) domain was intact in the cat but mutated in the dog. The DNA and ligand-binding domains were highly similar among the species. In cats with fibroadenomatous hyperplasia (FAH), high expression of PR mRNA together with growth hormone (GH), GH receptor (GHR) and IGF-I mRNA was found in comparison with feline mammary carcinomas. Immunohistochemical analysis showed strong nuclear as well as cytoplasmic staining for PR in FAH. Western blot analysis revealed expression of the PR-A and PR-B isoforms in the feline mammary gland. In canine mammary tissue, the most abundant PR staining was found in proliferative zones of the mammary gland. Western blot analyses showed mainly staining for PR-A with lower PR-B staining. It is concluded that in dogs and cats both PR isoforms are expressed. The role of mutations found in the canine PR-B is discussed.

Beyond triple-negative breast cancer: the need to define new subtypes.

Advances in the systemic treatment of early breast cancer have led to significant improvements in survival for patients with hormone receptor- and/or HER2-positive disease. In recent years, interest has focused on tumors that lack expression of the estrogen receptor, progesterone receptor and HER2, the so-called triple-negative subgroup. As a group, triple-negative cancers have a relatively aggressive clinical course, with early development of visceral metastases and a poor long-term prognosis. These tumors, however, encompass a wide range of subtypes with varying prognosis, including a number of special types with a good prognosis (e.g., adenoid cystic carcinomas and secretory carcinoma). There is considerable overlap between triple-negative and basal-like tumors; however, microarray studies have demonstrated that the overlap between basal-like and triple-negative cancers is not complete. The similarities between sporadic triple-negative cancers and tumors arising in BRCA1 mutation carriers and the fact that the majority of BRCA1 tumors display a triple-negative phenotype have led to studies demonstrating a potential loss of BRCA1 function in triple-negative cancers and offered potential therapeutic avenues for patients with these cancers. However, it should be noted that triple-negative breast cancers comprise a heterogeneous group of tumors. Understanding the molecular underpinning of distinct subgroups of these cancers is crucial for the identification of novel therapeutic targets and individualization of treatment for patients with triple-negative disease.

Molecular cloning and expression of progestin membrane receptor component 1 (Pgmrc1) of the giant tiger shrimp Penaeus monodon.

Knowledge on molecular mechanisms of steroid hormonal induction on oocyte development may lead to the possible ways to effectively induce ovarian maturation in shrimp. In this study, progestin membrane receptor component 1 (Pgmrc1) of the giant tiger shrimp (Penaeus monodon) initially identified by EST analysis was further characterized. The full-length cDNA of Pgmrc1 was 2015bp in length containing an ORF of 573bp corresponding to a polypeptide of 190 amino acids. Northern blot analysis revealed a single form of Pgmrc1 in ovaries of P. monodon. Quantitative real-time PCR indicated that the expression level of Pgmrc1 mRNA in ovaries of both intact and eyestalk-ablated broodstock was greater than that of juveniles (P<0.05). Pgmrc1 was up-regulated in mature (stage IV) ovaries of intact broodstock (P<0.05). Unilateral eyestalk ablation resulted in an earlier up-regulation of Pgmrc1 since the vitellogenic (II) ovarian stage. Moreover, the expression level of Pgmrc1 in vitellogenic, early cortical rod and mature (II-IV) ovaries of eyestalk-ablated broodstock was greater than that of the same ovarian stages in intact broodstock (P<0.05). Pgmrc1 mRNA was clearly localized in the cytoplasm of follicular cells, previtellogenic and early vitellogenic oocytes. Immunohistochemistry revealed the positive signals of the Pgmrc1 protein in the follicular layers and cell membrane of follicular cells and various stages of oocytes. Taken the information together, Pgmrc1 gene products seem to play the important role on ovarian development and may be used as the bioindicator for monitoring progression of oocyte maturation of P. monodon.

Estrogen and progesterone receptors: from molecular structures to clinical targets.

Research involving estrogen and progesterone receptors (ER and PR) have greatly contributed to our understanding of cell signaling and transcriptional regulation. In addition to the classical ER and PR nuclear actions, new signaling pathways have recently been identified due to ER and PR association with cell membranes and signal transduction proteins. Bio-informatics has unveiled how ER and PR recognize their ligands, selective modulators and co-factors, which has helped to implement them as key targets in the treatment of benign and malignant tumors. Knowledge regarding ER and PR is vast and complex; therefore, this review will focus on their isoforms, signaling pathways, co-activators and co-repressors, which lead to target gene regulation. Moreover it will highlight ER and PR involvement in benign and malignant diseases as well as pharmacological substances influencing cell signaling and provide established and new structural insights into the mechanism of activation and inhibition of these receptors.

Progestin receptor subtypes in the brain: the known and the unknown.

Progesterone (P), the most biologically active progestin of ovarian origin, modulates numerous cellular functions in the central nervous system to coordinate physiology and reproduction. The neurobiological activity of P is mediated not by a single form of the progestin receptor (PR), but by two neural isoforms of PRs, PR-A and PR-B. Classical model of P action assumes that these neural effects are primarily mediated via their intracellular PRs, acting as transcriptional regulators, in steroid-sensitive neurons, modulating genes and genomic networks. Evidence has emerged, however, that activation of neural PRs is much more diverse; four distinct classes of molecules, neurotransmitters, peptide growth factors, cyclic nucleotides, and neurosteroids have been shown to activate the PRs via cross-talk and pathway convergence. In addition, rapid signaling events associated with membrane receptors and/or subpopulations of cytoplasmic PRs, via activation of protein kinase cascades, regulate PR gene expression in the cytoplasm independent of PR nuclear action. The increasing in vitro and in vivo evidence of differential transcriptional activities and coregulator interactions between PR-A and PR-B predict that these isoforms could have distinct roles in mediating additional and/or alternate signaling pathways within steroid-sensitive neurons. In this minireview, we evaluate the available data and discuss the possible roles of the isoforms in the regulation of neurobiological processes.

Progesterone receptor isoforms profile, modulate matrix metalloproteinase 2 expression in the decidua.

OBJECTIVE: This study explores the effect of progesterone and the role of the progesterone receptor (PR) profile on matrix metalloproteinase (MMP)-2 expression in human decidua. STUDY DESIGN: Zymography was conducted for MMP secretion. Semiquantitative reverse transcriptase-polymerase chain reaction was performed to examine MMP2 transcripts. Progesterone's effect on the MMP2 promoter was determined testing luciferase activity. The role of PR isoform on MMP2 expression was studied using human PR complementary DNA encoding PR isoforms PRA, PRB, or PRC. RESULTS: In decidua with overexpressed PRB, progesterone decreased MMP2 expression. Progesterone increased pro-MMP2 expression in decidua with overexpressed PRA or PRC. MMP2 promoter activity was unchanged following transfection with human PRA in the absence or presence of progesterone. Decreased promoter activity was observed following transfection with human PRB or human PRC. Progesterone increased promoter activity with overexpressed human PRC. CONCLUSION: Progesterone hampers MMP2 expression in the decidua via PRB. PRA has a repressive effect on PRB, whereas PRC seems to have a repressive effect on both PRA and PRB.

Body size and risk for breast cancer in relation to estrogen and progesterone receptor status in Japan.

PURPOSE: The aim of this study is to examine the association of height, weight, and body mass index (BMI) with breast cancer and its hormone receptor-defined subtype in a low-risk population. METHODS: We identified 441 newly diagnosed cases of breast cancer during a 9.9-year follow-up of a population-based cohort consisting of 55,537 women aged 40 to 69 years. Body size was assessed by using a self-administered questionnaire. RESULTS: We found a significant positive association of height and marginally significant positive associations of weight and BMI with breast cancer in postmenopausal women. Weight and BMI were associated more strongly with estrogen receptor-positive (ER+) than ER-negative (ER-) breast cancer in postmenopausal women. BMI was related significantly to increased risk for ER+ (hazard ratio [HR] per BMI increment of 1 kg/m2, 1.08; 95% confidence interval [CI], 1.01-1.15), but not ER- breast cancer (HR per BMI increment of 1 kg/m2, 0.95; 95% CI, 0.84-1.06; p for difference of HRs=0.048). CONCLUSIONS: The present study suggests that height, weight, and BMI are associated with increased risk for breast cancer among postmenopausal women in Japan. The positive association of weight and BMI might be limited to ER+ breast cancer.

Tissue- and hormone-dependent progesterone receptor distribution in the rat uterus.

BACKGROUND: Estradiol (E2) and progesterone (P) are well known regulators of progesterone receptor (PR) expression in the rat uterus. However, it is not known which receptor subtypes are involved. Little knowledge exist about possible differences in PR regulation through ERalpha or ERbeta, and whether the PR subtypes are differently regulated depending on ER type bound. Thus, in the present study PR immunostaining has been examined in uteri of ovariectomized (ovx) rats after different treatments of estrogen and P, in comparison with that in immature, cycling, and pregnant animals. METHODS: The uteri were collected from 1) ovx rats treated with E2 and/or P; 2) immature rats, intact cycling rats and animals pregnant day 8 and 18; 3) ovx rats treated with E2 or an estrogen receptor (ER)alpha agonist or an ERbeta agonist. Two antibodies were used, one detecting PRA+B and another one specific for PRB. Real-time PCR was used to determine mRNA levels for PRAB and PRB in experiment 3. RESULTS: In stroma and myometrium faint staining was detected in ovx controls (OvxC), whereas E2 treatment resulted in strong staining. In contrast to this, in luminal epithelium (LE) the staining was strong in the OvxC group, whereas E2 treatment during the last 24 hrs before sacrifice caused a decrease. Similar to OvxC the LE of the immature animals was strongly stained. In the pregnant rats LE was negative, well in agreement with the results seen after E2 treatment. In the pregnant animals the stroma and decidua was strongly stained for PRAB, but only faint for PRB, indicating that PRA is the most expressed isoform in this state. The increase in stromal and myometrial immunostaining after E2 treatment was also found after treatment with the ERalpha agonist PPT. The ERbeta agonist DPN caused a decrease of the PR mRNA levels, which was also found for PRAB and PRB immunostaining in the GE. CONCLUSION: Stromal and myometrial PRAB levels are increased via ERalpha, as shown by treatment with E2 and the ERalpha agonist PPT, while the levels in LE are decreased. The uterine stroma of pregnant rats strongly expressed PRAB, but very little PRB, which is different to E2 treated ovx animals where both PRAB and PRB are strongly expressed. The ERbeta agonist DPN decreased the mRNA levels of PRAB and PRB, as well as the PRAB protein level in GE. These results suggest that ERbeta signals mainly down-regulate PR levels in the epithelial cells. ERalpha, on the other hand, up-regulates PR levels in the stroma and myometrium while it decreased them in LE. Thus, the effects from E2 and PPT on the mRNA levels, as determined by PCR, could be annihilated since they are increased and decreased depending on cell type. The distribution and amount of PR isoforms strongly depend on the hormonal milieu and cell type within the rat uterus.

Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers.

PURPOSE: The prognosis of a patient with estrogen receptor (ER) and/or progesterone receptor (PR) -positive breast cancer can be highly variable. Therefore, we developed a gene expression-based outcome predictor for ER+ and/or PR+ (ie, luminal) breast cancer patients using biologic differences among these tumors. MATERIALS AND METHODS: The ER+ MCF-7 breast cancer cell line was treated with 17beta-estradiol to identify estrogen-regulated genes. These genes were used to develop an outcome predictor on a training set of 65 luminal epithelial primary breast carcinomas. The outcome predictor was then validated on three independent published data sets. Results The estrogen-induced gene set identified in MCF-7 cells was used to hierarchically cluster a 65 tumor training set into two groups, which showed significant differences in survival (P = .0004). Supervised analyses identified 822 genes that optimally defined these two groups, with the poor-prognosis group IIE showing high expression of cell proliferation and antiapoptosis genes. The good prognosis group IE showed high expression of estrogen- and GATA3-regulated genes. Mean expression profiles (ie, centroids) created for each group were applied to ER+ and/or PR+ tumors from three published data sets. For all data sets, Kaplan-Meier survival analyses showed significant differences in relapse-free and overall survival between group IE and IIE tumors. Multivariate Cox analysis of the largest test data set showed that this predictor added significant prognostic information independent of standard clinical predictors and other gene expression-based predictors. CONCLUSION: This study provides new biologic information concerning differences within hormone receptor-positive breast cancers and a means of predicting long-term outcomes in tamoxifen-treated patients.

The progesterone receptor in human term amniochorion and placenta is isoform C.

The mechanism that initiates human parturition has been proposed to be functional progesterone withdrawal whereby the 116-kDa B isoform of the progesterone receptor (PR-B) switches in favor of the 94-kDa A isoform (PR-A) in reproductive tissues. Recently other PR isoforms, PR-S, PR-C, and PR-M generated from the same gene have been identified and partially characterized. Using immunohistochemical, Western blotting, and RT-PCR techniques, evidence is provided that the major PR isoform present in human term fetal membranes (amnion and chorion) and syncytiotrophoblast of the placenta is neither of the classical nuclear PR-B or PR-A isoforms but is the N terminally truncated 60-kDa PR-C isoform. Evidence is also provided that the PR-C isoform resides in the cytoplasm of the expressing cell types. Data are also presented to show that PR-B, PR-A, and PR-S isoforms are essentially absent from the amnion and chorion, whereas PR isoforms A, B, C, and S are all present in the decidua, with PR-A being the major isoform. The syncytiotrophoblast of the placenta contains the cytoplasmic PR-C isoform but not PR-A, PR-B, or PR-S. The major PR isoform in the amnion, chorion, and placenta is PR-C, suggesting that the cytoplasmic PR-C isoform has a specific role in extraembryonic tissues and may be involved in the regulation of human parturition.

Non-steroidal progesterone receptor specific ligands.

The nuclear receptor for progesterone is a target for contraception and for several therapeutic indications. Progestin agonists and antagonists in clinical use mimic the steroidal backbone of the cognate ligand, progesterone. Thus, they have significant cross-reactivity with other steroid receptors. Recently, non-steroidal progesterone receptor ligands have begun to appear in the literature. This review will describe the current status of research into these promising new chemical entities.

Progesterone receptors: various forms and functions in reproductive tissues.

The unequivocal role of progesterone in a variety of events like ovulation, mammary gland development, establishment and maintenance of pregnancy etc are well established. Also the data are accumulating on its role in male reproductive events. In vertebrates and humans, the biological activity of progesterone is mediated by two progesterone receptor proteins PR-A and PR-B, that arise from the same gene and are the members of nuclear receptor superfamily of transcriptional factors. Several studies have demonstrated that the blockage of progesterone receptor using antiprogestins impairs folliculogenesis, ovulation, implantation and pregnancy. Progesterone receptor (PR), have also been detected in human spermatozoa. However, unlike the conventional PR, sperm PR was localized on the membrane and showed distinct characteristics in terms of its size. There are data to demonstrate the inhibition of progesterone driven functions such as hyperactive motility, acrosome reaction on neutralization of sperm membrane PR with specific antibodies against PR. Further significant decrease in the % of PR positive spermatozoa was observed in infertile cases as compared to the fertile men. This indicated that PR can serve as the marker to define the fertilizing potential of the spermatozoa. Recently we have also shown that the PR is expressed in human testis. This reinforced that this PR protein is an inherent testicular protein and not a secretion of accessory reproductive organs. This review compiles the major observations on the forms of the progesterone receptor in various reproductive tissues.

Classic and non-classic progesterone receptors are both expressed in human spermatozoa.

Progesterone is one of the physiological inducers of the acrosome reaction in mammalian spermatozoa. The receptor that responds to progesterone is not yet identified, and its properties differ in many aspects from the properties of the classic nuclear progesterone receptor, suggesting the participation of a novel or non-classic receptor. In this study, we investigated the expression of a novel progesterone-binding protein (hmPR1/PGMRC1) and its ortholog (hmPR2/PGMRC2), which have previously been identified in liver microsomes and are considered receptor candidates, along with the nuclear progesterone receptor. The purification procedure was optimized with special emphasis on the control of leukocyte contamination in single donor samples. The results indicate that all three proteins are expressed in human sperm, as transcripts have been detected in 46 %, 42 % and 37.5 % of individual samples, respectively (n = 24).

Risk of breast cancer classified by joint estrogen receptor and progesterone receptor status among women 20-44 years of age.

To gain insight into whether breast cancer tumors jointly classified by estrogen receptor (ER) and progesterone receptor (PR) status represent diseases with differing etiologies, data from a population-based case-control study of US women 20-44 years of age were analyzed. Cases included 1,556 women diagnosed between 1990 and 1992. Age- and geographic-frequency-matched controls included 1,397 women identified by random digit dialing. Heterogeneity between ER+PR+ and ER-PR- tumors was most pronounced in relation to age, race, and recreational exercise at 12-13 years of age. Multivariate-adjusted odds ratios for ER+PR+ tumors were 0.64 (95% confidence interval (CI): 0.47, 0.89) for 30-34 versus 40-44 years of age, 0.89 (95% CI: 0.63, 1.25) for Black versus White race, and 0.84 (95% CI: 0.68, 1.03) for exercise at 12-13 years of age above versus at or below the median. Corresponding odds ratios for ER-PR- tumors were 1.24 (95% CI: 0.86, 1.77), 1.51 (95% CI: 1.07, 2.14), and 1.15 (95% CI: 0.90, 1.48). Risk of ER-PR- cancer in relation to menstrual and reproductive (parity and lactation) characteristics, alcohol consumption, and family history of breast cancer was similar to that observed for ER+PR+ tumors. These findings only modestly support the hypothesis that hormonally related risk factors have differing relations with ER+PR+ versus ER-PR- tumors among younger women.

Membrane-bound progesterone receptors coupled to G proteins in the fungus Rhizopus nigricans.

Steroid binding sites with high affinity for progesterone (Kd=40+/-14 nM determined by binding, and Kd=71+/-22 nM determined by displacement studies) and lower affinity for 21-hydroxyprogesterone and for testosterone, but no affinity for estradiol-17beta, onapristone and alpha-naphthoflavone were detected in the enriched plasma membrane fraction of the fungus Rhizopus nigricans. The amount of steroid binding sites is in accordance with the value of B(max)=744+/-151 fmol (mg protein)(-1). In the membrane fraction, progesterone induced about 30% activation of G proteins over basal level, as determined by GTPase activity (EC50=32+/-8 nM) and by the guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding rate (EC50=61+/-21 nM). The affinity of receptors for progesterone was substantially decreased in the presence of GTPgammaS and of cholera toxin. Our results suggest the existence of progesterone receptors in the membrane of Rhizopus nigricans and their coupling to G proteins.

G-protein coupled progesterone receptors in the plasma membrane of fungus Rhizopus nigricans.

We have demonstrated simultaneous existence of progesterone receptors and GTPase activity in the membranes prepared from the filamentous fungus Rhizopus nigricans. The results obtained with pertussis toxin treated fungal mycelium suggest that these receptors do not couple to Gi-Go-proteins and play a role in the induction of steroid hydroxylating enzyme system by steroid substrates in the fungus.