Konstantin Svechnikov - Academia.edu (original) (raw)
Papers by Konstantin Svechnikov
Genetika, 1993
A segregation analysis of inheritance of the blood serotonin level in a domesticated silver fox p... more A segregation analysis of inheritance of the blood serotonin level in a domesticated silver fox population was performed (104 foxes from 4 pedigrees). The results of the analysis point to the effect of a major-gene in the control of this quantitative trait (dominance coefficient of lower level is 0.79), and suggest that breeding for domestic behavior is accompanied by selection against heterozygosity with respect to this major-gene. The lower blood serotonin level revealed in more domesticated foxes (p < 0.02) may be a consequence of this.
Best Practice & Research Clinical Endocrinology & Metabolism, Feb 1, 2008
Sex steroids are crucial hormones for the proper development and function of the body; they regul... more Sex steroids are crucial hormones for the proper development and function of the body; they regulate sexual differentiation, the secondary sex characteristics, and sexual behaviour patterns. Gonads are the major sources of sex steroids, although adrenal cortex, placenta, and to a lesser extent other tissues contribute to their production in adult life and at various phases of development. Steroidogenesis of gonadal sex hormones is by definition sexually dimorphic, and involves differences not only in hormonal action but also in regulation and temporal patterns of production. This review focuses on the ontogeny and developmental regulation of steroid hormones in the gonads, with an attempt to detail these processes in humans.
Scripta scientifica medica, 2016
The Royal Society of Chemistry eBooks, Nov 4, 2011
Androgens produced by fetal Leydig cells (FLCs) during the masculinization programming window of ... more Androgens produced by fetal Leydig cells (FLCs) during the masculinization programming window of fetal development play a critical role in the proper development of the male phenotype. An increased incidence of human male reproductive developmental disorders has occurred during recent decades (e.g. cryptorchidism, hypospadia, testicular cancer) and has been proposed to be due to environmental influences, including adverse actions of endocrine disruptors (EDCs) on FLCs steroidogenesis. This review covers the different classes of EDCs, such as pesticides that act as androgen receptor antagonists, phthalates and dioxins, which appear to inhibit fetal testosterone synthesis, as well as estrogenic compounds. The effects of these compounds on steroidogenesis by Leydig cells and the reproductive development are reviewed and their possible role in connection with the increasing frequencies of abnormalities in reproductive development is discussed.
PLOS ONE, Aug 15, 2013
<p>Data are expressed as fold change ± S.E.M for four independent RNA preparations. *P<0... more <p>Data are expressed as fold change ± S.E.M for four independent RNA preparations. *P<0.05 compared to CBA/Lac.</p
Bulletin of Experimental Biology and Medicine, Aug 1, 1994
The function of Leydig's cells during stimulation of various components of the adenylate... more The function of Leydig's cells during stimulation of various components of the adenylatecyclase system was studied in inbred mice of various lines. Mice of different lines were found to differ markedly in their production of testosterone during stimulation of a crude Leydig's cell suspension with ascending concentrations of chorionic gonadotropin, cholera toxin, forskolin, and dibutyryl-cAMP. The ranking of the lines according to the maximal production of testosterone was virtually the same during exposure to steroidogenesis activators.
Molecular Nutrition & Food Research, Oct 4, 2016
Resveratrol has a diverse array of healthful effects on metabolic parameters in different experim... more Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal steroidogenesis at gestational weeks (GW) 9-12. Methods and results Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours. The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA), androstenedione and 11-deoxicortisol by ACTH-activated and unstimulated HFAC, which was associated with inhibition of the activities and expression of cytochromes 17αhydroxylase/17,20 lyase (CYP17) and 21-hydroxylase (CYP21) in these fetal adrenocortical cells. Conclusion Our in vitro findings on the sensitivity of human fetal adrenal steroidogenesis to resveratrol at GW9-12 suggest that intake of this polyphenol at high doses by women who are at early stages of pregnancy is undesirable.
Journal of Molecular Endocrinology, Feb 1, 2003
We have investigated the involvement of the steroidogenic acute regulatory (StAR) protein in inte... more We have investigated the involvement of the steroidogenic acute regulatory (StAR) protein in interleukin-1α (IL-1α)-induced steroidogenesis in immature (40-day-old) and adult Leydig cells in vitro. Further, IL-1α-mediated signaling pathway(s) controlling StAR expression in immature Leydig cells were also studied. IL-1α stimulated both androgen production and StAR protein expression in a dose-and time-dependent manner in immature but not adult Leydig cells. These effects of IL-1α were prevented by pretreatment of the cells with the specific inhibitors of the p38 MAP kinase, SB203580 and PD169316, suggesting that this kinase is an important part of IL-1α signaling in the immature Leydig cell. The present results suggest that IL-1α, which is constitutively produced by the rat testis from postnatal day 25, is an important paracrine regulator of postnatal Leydig cell maturation. Regulation of StAR protein expression is one of the possible mechanisms by which IL-1α contributes to the differentiation of immature Leydig cells into adult cells.
Cytokine, Oct 7, 2005
We have reported earlier that interleukin-1 (IL-1) is a potent growth factor for immature Sertoli... more We have reported earlier that interleukin-1 (IL-1) is a potent growth factor for immature Sertoli cells (somatic cells in the testis required for testicular development and later spermatogenesis) and that this effect is synergistic with the mitogenic effect of follicle-stimulating hormone (FSH). The aim of the present study was to determine whether MAPK pathways are involved in mediating the mitogenic effect of IL-1 on Sertoli cells. Western blotting revealed that IL-1alpha activated p38 MAPK and JNK/SAPK, but not ERK, in Sertoli cells from 8- or 9-day-old rat. The inhibitor of p38 MAPK SB203580 attenuated the IL-1alpha-induced proliferation of Sertoli cells, as assessed by (3)H-thymidine incorporation and supravital staining as well as by direct cell counting. We conclude that the p38 MAPK pathway mediates the proliferative effect of IL-1alpha on immature Sertoli cells in vitro. Since the mitogenic effect of FSH is mediated via ERK, the synergistic action of IL-1alpha and FSH may be explained by their different intracellular signalling pathways. Induction of IL-1 by inflammation, infection or other tissue injuries may result in testicular damage by interfering with normal Sertoli cell development and thus future spermatogenesis.
Journal of Applied Toxicology, Nov 1, 2009
Resveratrol and its analogs are considered to be a promising drug candidate for treatment of canc... more Resveratrol and its analogs are considered to be a promising drug candidate for treatment of cancer and different age-associated diseases. In the present study we have investigated the effects of resveratrol and its synthetic analogs on steroidogenesis and mitochondrial function in primary cultures of rat Leydig cells. Our findings indicate that resveratrol and its analogs structure-dependently attenuated hCG-activated steroidogenesis in Leydig cells through suppression of the expression of steroidogenic acute regulatory protein and cytochrome P450c17. 3,5-Diacetyl resveratrol was observed to modulate mitochondrial function in Leydig cells, suppressing polarization of inner mitochondrial membrane, and 3,4,4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-trimethoxystilbene stimulated the overall activity of intracellular reductases involved in the reduction of WST-1 to formazan. Thus, the inhibitory actions of resveratrol analogs on steroidogenesis in Leydig cells indicate novel mechanisms of action of these compounds, which may be of potential therapeutic interest, where suppression of androgen action is needed.
Endocrinology, Oct 1, 2004
Hormone Research in Paediatrics, 2010
Sex steroids are crucial regulators of sexual differentiation and the proper development of secon... more Sex steroids are crucial regulators of sexual differentiation and the proper development of secondary sex characteristics and patterns of sexual behavior. Since Leydig cells are the primary major producers of these steroid hormones, maintenance of the normal functions of these cells determines the reproductive capacity and fertility of males. The present minireview discusses recent findings concerning endocrine and paracrine regulation of the proliferation, differentiation and involution of human Leydig cells. The physiology and function of the two distinct fetal and adult populations of human Leydig cells are described, with particular focus on the paracrine environment that triggers their differentiation and functional maturation. The roles of established and more recently discovered paracrine regulators of this maturation, including insulin-like factor 3, platelet-derived growth factor-␣ , desert hedgehog, ghrelin and leptin are considered. A brief description of the origin, ontogenesis and functional markers of human fetal and adult Leydig cells is presented.
57th Annual ESPE, Aug 28, 2018
55th ESPE Meeting, Aug 19, 2016
54th Annual ESPE, Aug 26, 2015
Reproduction, Fertility and Development, 2019
Hormone Research in Paediatrics, 2005
Background and Aim: The phytoestrogen resveratrol is found in grapes, mulberries and peanuts, all... more Background and Aim: The phytoestrogen resveratrol is found in grapes, mulberries and peanuts, all of which are consumed regularly by humans. Resveratrol is also used in chemotherapy against cancer and aging and as a cardioprotectant. The aim of the present study was to characterize the effects of resveratrol on rat adrenal steroidogenesis and to study the underlying mechanism. Methods: Adrenocortical cells were isolated from the adrenal glands of normal male rats (in vitro) and from male rats administered resveratrol in their diet for 12 weeks (ex vivo). Cells from resveratrol-treated and non-treated rats were tested ex vivo for responsiveness to ACTH and cells from normal rats were tested in vitro for responsiveness to ACTH in the presence and absence of resveratrol. Corticosterone and progesterone production were measured by RIA and expression of steroidogenic enzymes analyzed by PAGE/Western blotting. Results: Corticosterone production was inhibited 47% by 50 µM resveratrol in vitro and 20% ex vivo, while progesterone production was elevated to 400% of the control value in in vitro experiments. Resveratrol treatment decreased adrenal cytochrome P450 c21-hydroxylase expression in vivo and cell culture conditions. No changes in cell viability or morphology were caused by exposure to resveratrol in both ex vivo and in vitro experiments. Conclusion: Resveratrol suppresses corticosterone production by primary rat adrenocortical cell cultures in vitro and ex vivo by inhibiting cytochrome P450 c21-hydroxylase.
Journal of Endocrinology, 2007
Reproductive Toxicology, Nov 1, 2006
Helenalin is a potent anti-inflammatory and anti-neoplastic agent isolated from several plant spe... more Helenalin is a potent anti-inflammatory and anti-neoplastic agent isolated from several plant species of the Asteracea family. Here, we have investigated the effects of helenalin on steroidogenesis activated by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) in primary cultures of rat adrenocortical and Leydig cells. Our findings demonstrate that helenalin inhibits both ACTH- and hCG-activated steroidogenesis in these cells. This effect was already evident after 2-3 h treatment with helenalin. In contrast, steroidogenesis from 22R-OHC, a cell-permeable form of cholesterol, was not inhibited by helenalin, suggesting that the expression of the steroidogenic acute regulartory (StAR) protein might be inhibited by this compound. Indeed, helenalin attenuated StAR protein expression activated by ACTH and hCG in adrenocortical and Leydig cells as assessed by PAGE/Western analyses. This inhibitory action of helenalin on steroidogenic cell functions indicates novel mechanisms of action of this compound which may be of potential therapeutic interest. However, it also poses safety concerns relating to possible negative side-effects on anabolism and systemic stress.
Steroids, 2019
The onset of steroidogenesis in human fetal testes (HFT) during the first trimester is poorly inv... more The onset of steroidogenesis in human fetal testes (HFT) during the first trimester is poorly investigated. One important unresolved question is the ontogeny of steroidogenic enzymes and formation of steroidogenic pathways in the HFT at early pregnancy. Our aim was to explore steroidogenesis, the expression of steroidogenic enzymes and their maturation in the HFT at gestational weeks (GW) 8-12. Steroids in the HFT were analyzed by gas chromatography/coupled to tandem mass spectrometry. The expression of steroidogenic enzymes in the HFT at GW8-12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that the HFT at GW8-9 produced low level of testosterone via the Δ 4 pathway and progesterone was the major steroid found in the testicular tissue. In contrast, more mature Leydig cells from the HFT at GW11-12 synthesized high levels of androgens via the Δ 5 pathway. We also observed a significant upregulation of the expression of StAR, CYP11A1, CYP17A1 and its accessory proteins, P450 oxidoreductase (POR) and cytochrome b5 in the HFT at GW11-12 compared to GW8-9. Altogether, our data suggest that that human fetal Leydig cells differentiate rapidly at the end of the first trimester by acquiring capacity to express high levels of steroidogenic enzymes and switch from the Δ 4 to the Δ 5 pathways to synthesize high levels of androgens due to maturation of the CYP17-POR-b5 complex.
Genetika, 1993
A segregation analysis of inheritance of the blood serotonin level in a domesticated silver fox p... more A segregation analysis of inheritance of the blood serotonin level in a domesticated silver fox population was performed (104 foxes from 4 pedigrees). The results of the analysis point to the effect of a major-gene in the control of this quantitative trait (dominance coefficient of lower level is 0.79), and suggest that breeding for domestic behavior is accompanied by selection against heterozygosity with respect to this major-gene. The lower blood serotonin level revealed in more domesticated foxes (p < 0.02) may be a consequence of this.
Best Practice & Research Clinical Endocrinology & Metabolism, Feb 1, 2008
Sex steroids are crucial hormones for the proper development and function of the body; they regul... more Sex steroids are crucial hormones for the proper development and function of the body; they regulate sexual differentiation, the secondary sex characteristics, and sexual behaviour patterns. Gonads are the major sources of sex steroids, although adrenal cortex, placenta, and to a lesser extent other tissues contribute to their production in adult life and at various phases of development. Steroidogenesis of gonadal sex hormones is by definition sexually dimorphic, and involves differences not only in hormonal action but also in regulation and temporal patterns of production. This review focuses on the ontogeny and developmental regulation of steroid hormones in the gonads, with an attempt to detail these processes in humans.
Scripta scientifica medica, 2016
The Royal Society of Chemistry eBooks, Nov 4, 2011
Androgens produced by fetal Leydig cells (FLCs) during the masculinization programming window of ... more Androgens produced by fetal Leydig cells (FLCs) during the masculinization programming window of fetal development play a critical role in the proper development of the male phenotype. An increased incidence of human male reproductive developmental disorders has occurred during recent decades (e.g. cryptorchidism, hypospadia, testicular cancer) and has been proposed to be due to environmental influences, including adverse actions of endocrine disruptors (EDCs) on FLCs steroidogenesis. This review covers the different classes of EDCs, such as pesticides that act as androgen receptor antagonists, phthalates and dioxins, which appear to inhibit fetal testosterone synthesis, as well as estrogenic compounds. The effects of these compounds on steroidogenesis by Leydig cells and the reproductive development are reviewed and their possible role in connection with the increasing frequencies of abnormalities in reproductive development is discussed.
PLOS ONE, Aug 15, 2013
<p>Data are expressed as fold change ± S.E.M for four independent RNA preparations. *P<0... more <p>Data are expressed as fold change ± S.E.M for four independent RNA preparations. *P<0.05 compared to CBA/Lac.</p
Bulletin of Experimental Biology and Medicine, Aug 1, 1994
The function of Leydig's cells during stimulation of various components of the adenylate... more The function of Leydig's cells during stimulation of various components of the adenylatecyclase system was studied in inbred mice of various lines. Mice of different lines were found to differ markedly in their production of testosterone during stimulation of a crude Leydig's cell suspension with ascending concentrations of chorionic gonadotropin, cholera toxin, forskolin, and dibutyryl-cAMP. The ranking of the lines according to the maximal production of testosterone was virtually the same during exposure to steroidogenesis activators.
Molecular Nutrition & Food Research, Oct 4, 2016
Resveratrol has a diverse array of healthful effects on metabolic parameters in different experim... more Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal steroidogenesis at gestational weeks (GW) 9-12. Methods and results Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours. The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA), androstenedione and 11-deoxicortisol by ACTH-activated and unstimulated HFAC, which was associated with inhibition of the activities and expression of cytochromes 17αhydroxylase/17,20 lyase (CYP17) and 21-hydroxylase (CYP21) in these fetal adrenocortical cells. Conclusion Our in vitro findings on the sensitivity of human fetal adrenal steroidogenesis to resveratrol at GW9-12 suggest that intake of this polyphenol at high doses by women who are at early stages of pregnancy is undesirable.
Journal of Molecular Endocrinology, Feb 1, 2003
We have investigated the involvement of the steroidogenic acute regulatory (StAR) protein in inte... more We have investigated the involvement of the steroidogenic acute regulatory (StAR) protein in interleukin-1α (IL-1α)-induced steroidogenesis in immature (40-day-old) and adult Leydig cells in vitro. Further, IL-1α-mediated signaling pathway(s) controlling StAR expression in immature Leydig cells were also studied. IL-1α stimulated both androgen production and StAR protein expression in a dose-and time-dependent manner in immature but not adult Leydig cells. These effects of IL-1α were prevented by pretreatment of the cells with the specific inhibitors of the p38 MAP kinase, SB203580 and PD169316, suggesting that this kinase is an important part of IL-1α signaling in the immature Leydig cell. The present results suggest that IL-1α, which is constitutively produced by the rat testis from postnatal day 25, is an important paracrine regulator of postnatal Leydig cell maturation. Regulation of StAR protein expression is one of the possible mechanisms by which IL-1α contributes to the differentiation of immature Leydig cells into adult cells.
Cytokine, Oct 7, 2005
We have reported earlier that interleukin-1 (IL-1) is a potent growth factor for immature Sertoli... more We have reported earlier that interleukin-1 (IL-1) is a potent growth factor for immature Sertoli cells (somatic cells in the testis required for testicular development and later spermatogenesis) and that this effect is synergistic with the mitogenic effect of follicle-stimulating hormone (FSH). The aim of the present study was to determine whether MAPK pathways are involved in mediating the mitogenic effect of IL-1 on Sertoli cells. Western blotting revealed that IL-1alpha activated p38 MAPK and JNK/SAPK, but not ERK, in Sertoli cells from 8- or 9-day-old rat. The inhibitor of p38 MAPK SB203580 attenuated the IL-1alpha-induced proliferation of Sertoli cells, as assessed by (3)H-thymidine incorporation and supravital staining as well as by direct cell counting. We conclude that the p38 MAPK pathway mediates the proliferative effect of IL-1alpha on immature Sertoli cells in vitro. Since the mitogenic effect of FSH is mediated via ERK, the synergistic action of IL-1alpha and FSH may be explained by their different intracellular signalling pathways. Induction of IL-1 by inflammation, infection or other tissue injuries may result in testicular damage by interfering with normal Sertoli cell development and thus future spermatogenesis.
Journal of Applied Toxicology, Nov 1, 2009
Resveratrol and its analogs are considered to be a promising drug candidate for treatment of canc... more Resveratrol and its analogs are considered to be a promising drug candidate for treatment of cancer and different age-associated diseases. In the present study we have investigated the effects of resveratrol and its synthetic analogs on steroidogenesis and mitochondrial function in primary cultures of rat Leydig cells. Our findings indicate that resveratrol and its analogs structure-dependently attenuated hCG-activated steroidogenesis in Leydig cells through suppression of the expression of steroidogenic acute regulatory protein and cytochrome P450c17. 3,5-Diacetyl resveratrol was observed to modulate mitochondrial function in Leydig cells, suppressing polarization of inner mitochondrial membrane, and 3,4,4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-trimethoxystilbene stimulated the overall activity of intracellular reductases involved in the reduction of WST-1 to formazan. Thus, the inhibitory actions of resveratrol analogs on steroidogenesis in Leydig cells indicate novel mechanisms of action of these compounds, which may be of potential therapeutic interest, where suppression of androgen action is needed.
Endocrinology, Oct 1, 2004
Hormone Research in Paediatrics, 2010
Sex steroids are crucial regulators of sexual differentiation and the proper development of secon... more Sex steroids are crucial regulators of sexual differentiation and the proper development of secondary sex characteristics and patterns of sexual behavior. Since Leydig cells are the primary major producers of these steroid hormones, maintenance of the normal functions of these cells determines the reproductive capacity and fertility of males. The present minireview discusses recent findings concerning endocrine and paracrine regulation of the proliferation, differentiation and involution of human Leydig cells. The physiology and function of the two distinct fetal and adult populations of human Leydig cells are described, with particular focus on the paracrine environment that triggers their differentiation and functional maturation. The roles of established and more recently discovered paracrine regulators of this maturation, including insulin-like factor 3, platelet-derived growth factor-␣ , desert hedgehog, ghrelin and leptin are considered. A brief description of the origin, ontogenesis and functional markers of human fetal and adult Leydig cells is presented.
57th Annual ESPE, Aug 28, 2018
55th ESPE Meeting, Aug 19, 2016
54th Annual ESPE, Aug 26, 2015
Reproduction, Fertility and Development, 2019
Hormone Research in Paediatrics, 2005
Background and Aim: The phytoestrogen resveratrol is found in grapes, mulberries and peanuts, all... more Background and Aim: The phytoestrogen resveratrol is found in grapes, mulberries and peanuts, all of which are consumed regularly by humans. Resveratrol is also used in chemotherapy against cancer and aging and as a cardioprotectant. The aim of the present study was to characterize the effects of resveratrol on rat adrenal steroidogenesis and to study the underlying mechanism. Methods: Adrenocortical cells were isolated from the adrenal glands of normal male rats (in vitro) and from male rats administered resveratrol in their diet for 12 weeks (ex vivo). Cells from resveratrol-treated and non-treated rats were tested ex vivo for responsiveness to ACTH and cells from normal rats were tested in vitro for responsiveness to ACTH in the presence and absence of resveratrol. Corticosterone and progesterone production were measured by RIA and expression of steroidogenic enzymes analyzed by PAGE/Western blotting. Results: Corticosterone production was inhibited 47% by 50 µM resveratrol in vitro and 20% ex vivo, while progesterone production was elevated to 400% of the control value in in vitro experiments. Resveratrol treatment decreased adrenal cytochrome P450 c21-hydroxylase expression in vivo and cell culture conditions. No changes in cell viability or morphology were caused by exposure to resveratrol in both ex vivo and in vitro experiments. Conclusion: Resveratrol suppresses corticosterone production by primary rat adrenocortical cell cultures in vitro and ex vivo by inhibiting cytochrome P450 c21-hydroxylase.
Journal of Endocrinology, 2007
Reproductive Toxicology, Nov 1, 2006
Helenalin is a potent anti-inflammatory and anti-neoplastic agent isolated from several plant spe... more Helenalin is a potent anti-inflammatory and anti-neoplastic agent isolated from several plant species of the Asteracea family. Here, we have investigated the effects of helenalin on steroidogenesis activated by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) in primary cultures of rat adrenocortical and Leydig cells. Our findings demonstrate that helenalin inhibits both ACTH- and hCG-activated steroidogenesis in these cells. This effect was already evident after 2-3 h treatment with helenalin. In contrast, steroidogenesis from 22R-OHC, a cell-permeable form of cholesterol, was not inhibited by helenalin, suggesting that the expression of the steroidogenic acute regulartory (StAR) protein might be inhibited by this compound. Indeed, helenalin attenuated StAR protein expression activated by ACTH and hCG in adrenocortical and Leydig cells as assessed by PAGE/Western analyses. This inhibitory action of helenalin on steroidogenic cell functions indicates novel mechanisms of action of this compound which may be of potential therapeutic interest. However, it also poses safety concerns relating to possible negative side-effects on anabolism and systemic stress.
Steroids, 2019
The onset of steroidogenesis in human fetal testes (HFT) during the first trimester is poorly inv... more The onset of steroidogenesis in human fetal testes (HFT) during the first trimester is poorly investigated. One important unresolved question is the ontogeny of steroidogenic enzymes and formation of steroidogenic pathways in the HFT at early pregnancy. Our aim was to explore steroidogenesis, the expression of steroidogenic enzymes and their maturation in the HFT at gestational weeks (GW) 8-12. Steroids in the HFT were analyzed by gas chromatography/coupled to tandem mass spectrometry. The expression of steroidogenic enzymes in the HFT at GW8-12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that the HFT at GW8-9 produced low level of testosterone via the Δ 4 pathway and progesterone was the major steroid found in the testicular tissue. In contrast, more mature Leydig cells from the HFT at GW11-12 synthesized high levels of androgens via the Δ 5 pathway. We also observed a significant upregulation of the expression of StAR, CYP11A1, CYP17A1 and its accessory proteins, P450 oxidoreductase (POR) and cytochrome b5 in the HFT at GW11-12 compared to GW8-9. Altogether, our data suggest that that human fetal Leydig cells differentiate rapidly at the end of the first trimester by acquiring capacity to express high levels of steroidogenic enzymes and switch from the Δ 4 to the Δ 5 pathways to synthesize high levels of androgens due to maturation of the CYP17-POR-b5 complex.