Female sexual behaviors in rodents (lordosis and appetitive or "proceptive" behaviors) are induced through a genomic mechanism by the sequential actions of estradiol (E2) and progesterone (P), or E2 and testosterone (T) at their respective receptors. However, non-steroidal agents, such as gonadotropin-releasing hormone (GnRH), Prostaglandin E2 (PGE2), noradrenaline, dopamine, oxytocin, α-melanocyte stimulating hormone, nitric oxide, leptin, apelin, and others, facilitate different aspects of female sexual behavior through their cellular and intracellular effects at the membrane and genomic levels in ovariectomized rats primed with E2. These neurotransmitters often act as intermediaries of E2 and P (or T). The classical model of steroid hormone action through intracellular receptor binding has been complemented by an alternative scenario wherein the steroid functions as a transcription factor after binding the receptor protein to DNA. Another possible mechanism occurs through the activation of second messenger systems (cyclic AMP, cyclic GMP, calcium), which subsequently initiate phosphorylation events via diverse kinase systems (protein kinases A, G, or C). These kinases target the progesterone receptor (PR) or associated effector proteins that connect the PR to the trans-activation machinery. This may also happen to the androgen receptor (AR). In addition, other cellular mechanisms could be involved since the chemical structure of these non-steroidal agents causes a change in their lipophobicity that prevents them from penetrating the cell and exerting direct transcriptional effects; however, they can exert effects on different components of the cell membrane activating a cross-talk between the cell membrane and the regulation of the transcriptional mechanisms.
- MeSH
- Rodentia MeSH
- Gonadal Steroid Hormones metabolism pharmacology MeSH
- Progesterone pharmacology metabolism MeSH
- Sexual Behavior, Animal * drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Biotransformation of steroids by fungi has been raised as a successful, eco-friendly, and cost-effective biotechnological alternative for chemical derivatization. Endophytic fungi live inside vegetal tissues without causing damage to the host plant, making available unique enzymes that carry out uncommon reactions. Moreover, using nanofibrous membranes as support for immobilizing fungal cells is a powerful strategy to improve their performance by enabling the combined action of adsorption and transformation processes, along with increasing the stability of the fungal cell. In the present study, we report the use of polyacrylonitrile nanofibrous membrane (PAN NFM) produced by electrospinning as supporting material for immobilizing the endophytic fungus Penicillium citrinum H7 aiming the biotransformation of progesterone. The PAN@H7 NFM displayed a high progesterone transformation efficiency (above 90%). The investigation of the biotransformation pathway of progesterone allowed the putative structural characterization of its main fungal metabolite by GC-MS analysis. The oxidative potential of P. citrinum H7 was selective for the C-17 position of the steroidal nucleus.
- MeSH
- Biotransformation MeSH
- Nanofibers * chemistry MeSH
- Progesterone MeSH
- Publication type
- Journal Article MeSH
The potential of microRNAs to protect the female reproductive system from the toxic influence of oil-related environmental contaminants has not yet been examined. The aim of the present study was to examine the ability of the microRNA miR-152 to prevent the toxic effects of toluene on ovarian cells. Porcine ovarian granulosa cells transfected or not transfected with miR-152 mimics were cultured with or without toluene (0, 10 and 100 ng/ml). The expression of miR-152; cell viability; proliferation (accumulation of PCNA, cyclin B1 and BrdU); cytoplasmic/mitochondrial apoptosis (accumulation of bax and caspase 3); and release of progesterone, testosterone and estradiol were quantified via RT-qPCR, the Trypan blue exclusion test, quantitative immunocytochemistry, the BrdU assay and ELISA. The addition of toluene reduced cell viability, decreased the levels of all the measured markers of proliferation and the release of all the measured steroid hormones, and promoted the expression of apoptosis markers. Transfection of cells with miR-152 mimics increased the expression of miR-152, cell proliferation, and progesterone release but reduced apoptosis and the release of testosterone and estradiol. Moreover, miR-152 prevented or inhibited all the toluene effects in addition to its inhibitory effect on testosterone and estradiol release. The present results demonstrate that miR-152 can protect ovarian cells from the harmful influence of toluene.
- MeSH
- Apoptosis * drug effects MeSH
- Estradiol MeSH
- Granulosa Cells * drug effects metabolism MeSH
- Cells, Cultured MeSH
- MicroRNAs * metabolism genetics MeSH
- Swine MeSH
- Progesterone metabolism MeSH
- Cell Proliferation drug effects MeSH
- Toluene * toxicity MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Endogenous neurosteroids (NS) and their synthetic analogs, neuroactive steroids (NAS), are potentially useful drug-like compounds affecting the pathophysiology of miscellaneous central nervous system disorders (e.g. Alzheimer ́s disease, epilepsy, depression, etc.). Additionally, NS have been shown to promote neuron viability and neurite outgrowth upon injury. The molecular, structural and physicochemical basis of the NS effect on neurons is so far not fully understood, and the development of new, biologically relevant assays is essential for their comparative analysis and for assessment of their mechanism of action. Here, we report the development of a novel, plate-based, high-content in vitro assay for screening of NS and newly synthesized, 5β-reduced NAS for the promotion of postnatal neuron survival and neurite growth using fluorescent, postnatal mixed cortical neuron cultures isolated from thy1-YFP transgenic mice. The screen allows a detailed time course analysis of different parameters, such as the number of neurons or neurite lengths of 7-day, in vitro neuron cultures. Using the screen, we identify a new NAS, compound 42, that promotes the survival and growth of postnatal neurons significantly better than several endogenous NS (dehydroepiandrosterone, progesterone, and allopregnanolone). Interestingly, we demonstrate that compound 42 also promotes the proliferation of glia (in particular oligodendrocytes) and that the glial function is critical for its neuron growth support. Computational analysis of the biological data and calculated physicochemical properties of tested NS and NAS demonstrated that their biological activity is proportional to their lipophilicity. Together, the screen proves useful for the selection of neuron-active NAS and the comparative evaluation of their biologically relevant structural and physicochemical features.
- MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Neurites MeSH
- Neurons MeSH
- Neurosteroids * MeSH
- Oligodendroglia MeSH
- Progesterone pharmacology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The precise method of action of dienogest on the production and development of endometriosis lesions is unknown, and its controversial effect on endometrial thickness has been under investigation. In the following study the Dienogest's effects on the target animal's histology of female reproductive organs, including the tissues from the Fallopian tubes, ovaries, and uterus, as well as the impact of drug administration on the liver's enzymes and the drug's effects on triglycerides, body weight, and HbA1c, have all been studied. The findings of the following experiment indicated that there was no significant elevation of liver enzymes. The little to no elevation of the liver enzymes indicated that the drug did not induce stress on the hepatic cells and according to the subsequent experiment it is safe for clinical use. Moreover, after 10, 20, and 30 days of blood administration, the level of blood TG significantly decreased, and after 30 days of intake, the level of blood sugar significantly decreased. However, there were no appreciable changes after 10 and 20 days. After 30 days of treatment, the rats' weight also showed a very minor drop. In addition to it, the results of histological changes in the tissue in the following study represented that there were evident changes in the tissues which comprised of decline in blood circulation, fibrosis in tissues, and degeneration of follicles.
- Keywords
- dienogest,
- MeSH
- Histological Techniques MeSH
- Liver Function Tests methods instrumentation MeSH
- Liver enzymology drug effects MeSH
- Contraceptive Agents * pharmacology blood metabolism MeSH
- Models, Animal MeSH
- Rats, Sprague-Dawley MeSH
- Progesterone pharmacology blood metabolism MeSH
- Statistics as Topic MeSH
- Transaminases analysis blood drug effects MeSH
- Genitalia, Female * pathology drug effects MeSH
- Check Tag
- Female MeSH
- Publication type
- Clinical Study MeSH
- MeSH
- Dydrogesterone administration & dosage therapeutic use MeSH
- Estrogens administration & dosage therapeutic use MeSH
- Hormone Replacement Therapy MeSH
- Climacteric * psychology drug effects MeSH
- Levonorgestrel administration & dosage therapeutic use MeSH
- Humans MeSH
- Medroxyprogesterone Acetate administration & dosage therapeutic use MeSH
- Hot Flashes drug therapy MeSH
- Perimenopause MeSH
- Progesterone administration & dosage therapeutic use MeSH
- Receptors, Estrogen MeSH
- Selective Serotonin Reuptake Inhibitors administration & dosage therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
The present study examined the effect of medicinal plants - ginkgo, tribulus (puncture vine), and yucca - on ovarian functions and their response to the toxic influence of toluene. Therefore, we analyzed the effect of toluene with and without these plant extracts on cultured human ovarian granulosa cells. Cell viability and the release of progesterone, insulin-like growth factor I (IGF I), oxytocin, and prostaglandin F (PGF) were analyzed using the trypan blue test, enzyme immunoassay, and enzyme-linked immunosorbent assay, respectively. The ginkgo, tribulus and yucca were able to suppress ovarian cell viability and alter the release of hormones. Toluene suppressed cell viability and the release of PGF, but not of progesterone, IGF-I, or oxytocin. The negative effect of toluene on cell viability was prevented and even reversed by ginkgo and yucca, whereas its effect on PGF was prevented or inverted by all tested plant extracts. These findings (1) demonstrated the direct toxic effect of toluene on ovarian cells, (2) showed the direct effect of some medicinal plants on ovarian cell functions, and (3) demonstrated the ability of these plants to inhibit the effects of toluene and to act as natural protectors against the suppressive effect of toluene on female reproduction.
- MeSH
- Plants, Medicinal * MeSH
- Humans MeSH
- Oxytocin MeSH
- Progesterone MeSH
- Plant Extracts pharmacology MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The fast-track process to approve vaccines against COVID-19 has raised questions about their safety, especially in relation to fertility. Over the last 2 years, studies have appeared monitoring female fertility, especially from assisted reproduction centers or in animal experiments. However, studies monitoring healthy populations are still limited. The aim of our study was to monitor the relevant parameters of female fertility (sex and other steroids, LH, FSH, SHBG, Antimüllerian hormone and antral follicle count) before and then 2-4 months after the third dose of vaccination against COVID-19 in a group of 25 healthy fertile woman. In addition, anti-SARS-CoV-2 and anti-SARS-CoV-2S antibodies were determined. We did not observe significant changes in the measured parameters before and after the third dose of vaccination. By comparing levels of the analytes with antibodies indicating a prior COVID-19 infection, we found that women who had experienced the disease had statistically lower levels of estrone, estradiol, SHBG and 5α-dihydroprogesterone, and conversely, higher levels of androgen active dehydroepiandrosterone and dihydrotestosterone. Our results confirm that vaccination does not affect female fertility, and that what fertile women should be worried about is not vaccination, but rather COVID-19 infection itself.
- MeSH
- 20-alpha-Dihydroprogesterone MeSH
- Androgens MeSH
- Anti-Mullerian Hormone * MeSH
- COVID-19 * prevention & control MeSH
- Dehydroepiandrosterone MeSH
- Dihydrotestosterone MeSH
- Estradiol MeSH
- Estrone MeSH
- Fertility MeSH
- Follicle Stimulating Hormone MeSH
- Humans MeSH
- COVID-19 Vaccines MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Intracerebroventricular (ICV) administration of estradiol benzoate (E2B) and progesterone (P) induces intense lordosis behavior in ovariectomized rats primed peripherally with E2B. The present study tested the hypothesis that the Kisspeptin (Kiss) and melanin-concentrating hormone (MCH) pathways regulate female sexual behavior induced by these steroid hormones. In Experiment 1, we tested the relevance of the Kiss pathway by ICV infusion of its inhibitor, kiss-234, before administration of E2B or P in estrogen-primed rats. Lordosis induced by E2B alone or with the addition of P was reduced significantly at 30, 120, and 240 min. In Experiment 2, ICV infusion of MCH 30 min before E2B or P significantly reduced lordosis in rats primed with E2B alone. These data support the hypothesis that the Kiss and MCH pathways, which can release or modulate gonadotropin-releasing hormone (GnRH), are involved in E2B- and P-induced lordosis.
- MeSH
- Estradiol pharmacology MeSH
- Gonadotropin-Releasing Hormone pharmacology MeSH
- Kisspeptins pharmacology MeSH
- Rats MeSH
- Lordosis * chemically induced MeSH
- Ovariectomy MeSH
- Progesterone * pharmacology MeSH
- Sexual Behavior, Animal physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.
- MeSH
- Hormones MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Progesterone * pharmacology physiology MeSH
- Progestins * pharmacology therapeutic use MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
