Overden ve Sürrenalden Salgılanan Hormonlar, Androjenler
Özet
Kadın fizyolojisinde over ve adrenal kaynaklı steroid hormonlar, üreme sistemi başta olmak üzere birçok fizyolojik sürecin düzenlenmesinde temel belirleyiciler arasındadır. Östrojenler ve progesteron, endometrial siklusun senkronizasyonu, fertilitenin sürdürülmesi ve gebelik sürecinin desteklenmesinde merkezi roller üstlenirken; androjenler ise östrojen sentezinde öncül olmanın yanısıra, follikül gelişimi, endometrial proliferasyon ve doku onarımı gibi olaylarda doğrudan biyolojik etki göstermektedir. Bu yazıda, hormonların sentez yolları, taşıyıcı proteinlerle ilişkileri, reseptör düzeyindeki etkinlik mekanizmaları ve hedef dokularda gerçekleşen dönüşüm süreçleri ayrıntılı biçimde açıklanmıştır. Ayrıca, bu steroidlerin kardiyovasküler, hepatik, hematolojik ve nöroendokrin sistem fonksiyonları üzerindeki etkileri ele alınmıştır. Bu derleme, kadınlarda steroid hormonların fizyolojik ve sistemik etkilerine ilişkin mevcut bilgi birikimini kapsamlı biçimde sentezleyerek alana katkı sunmayı amaçlamaktadır.
Referanslar
Lee MM. Reproductive hormones in infant girls—a harbinger of adult reproductive function? : Oxford University Press; 2003. p. 3513-4.
Sehested A, Juul A, Andersson AM, Petersen JH, Jensen TK, Müller J, et al. Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels. The Journal of Clinical Endocrinology & Metabolism. 2000;85(4):1634-40.
Hobeika E, Armouti M, Kala HS, Stocco C. Ovarian hormones. Hormonal Signaling in Biology and Medicine: Elsevier; 2020. p. 565-83.
Simpson ER, editor Models of aromatase insufficiency. Seminars in reproductive medicine; 2004: Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New ….
Segawa T, Teramoto S, Omi K, Miyauchi O, Watanabe Y, Osada H. Changes in estrone and estradiol levels during follicle development: a retrospective large-scale study. Reproductive Biology and Endocrinology. 2015;13:1-7.
Canipari R. Oocyte–granulosa cell interactions. Human reproduction update. 2000;6(3):279-89.
Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis—some new perspectives. Endocrinology. 2001;142(11):4589-94.
Stocco C. Aromatase expression in the ovary: hormonal and molecular regulation. Steroids. 2008;73(5):473-87.
Monget P, Bondy C. Importance of the IGF system in early folliculogenesis. Molecular and cellular endocrinology. 2000;163(1-2):89-93.
Richards JS. Perspective: the ovarian follicle—a perspective in 2001. Endocrinology. 2001;142(6):2184-93.
Britt K, Findlay J. Estrogen actions in the ovary revisited. Journal of Endocrinology. 2002;175(2):269-76.
Marino M, Galluzzo P, Ascenzi P. Estrogen signaling multiple pathways to impact gene transcription. Current genomics. 2006;7(8):497-508.
Prossnitz ER, Barton M. The G-protein-coupled estrogen receptor GPER in health and disease. Nature Reviews Endocrinology. 2011;7(12):715-26.
Otto C, Fuchs I, Kauselmann G, Kern H, Zevnik B, Andreasen P, et al. GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biology of reproduction. 2009;80(1):34-41.
Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Human reproduction update. 2014;20(4):485-500.
Wang H, Eriksson Hk, Sahlin L. Estrogen receptors α and β in the female reproductive tract of the rat during the estrous cycle. Biology of reproduction. 2000;63(5):1331-40.
Winuthayanon W, Bernhardt ML, Padilla-Banks E, Myers PH, Edin ML, Lih FB, et al. Oviductal estrogen receptor α signaling prevents protease-mediated embryo death. elife. 2015;4:e10453.
Orihuela PA, Croxatto HB. Acceleration of oviductal transport of oocytes induced by estradiol in cycling rats is mediated by nongenomic stimulation of protein phosphorylation in the oviduct. Biology of Reproduction. 2001;65(4):1238-45.
Zhu L, Pollard JW. Estradiol-17β regulates mouse uterine epithelial cell proliferation through insulin-like growth factor 1 signaling. Proceedings of the National Academy of Sciences. 2007;104(40):15847-51.
Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science. 2005;308(5728):1583-7.
Scarabin P-Y. Hormones and venous thromboembolism among postmenopausal women. Climacteric. 2014;17(sup2):34-7.
Syan SK, Minuzzi L, Costescu D, Smith M, Allega OR, Coote M, et al. Influence of endogenous estradiol, progesterone, allopregnanolone, and dehydroepiandrosterone sulfate on brain resting state functional connectivity across the menstrual cycle. Fertility and sterility. 2017;107(5):1246-55. e4.
Filicori M, Butler JP, Crowley W. Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion. The Journal of clinical investigation. 1984;73(6):1638-47.
Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocrine reviews. 2007;28(1):117-49.
Condon JC, Hardy DB, Kovaric K, Mendelson CR. Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-κB may contribute to the onset of labor through inhibition of PR function. Molecular endocrinology. 2006;20(4):764-75.
Garg D, Ng SSM, Baig KM, Driggers P, Segars J. Progesterone-mediated non-classical signaling. Trends in Endocrinology & Metabolism. 2017;28(9):656-68.
Devoto L, Vega M, Kohen P, Castro O, Carvallo P, Palomino A. Molecular regulation of progesterone secretion by the human corpus luteum throughout the menstrual cycle. Journal of reproductive immunology. 2002;55(1-2):11-20.
Duffy DM, Chaffin CL, Stouffer RL. Expression of estrogen receptor α and β in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone. Endocrinology. 2000;141(5):1711-7.
Peluso JJ. Progesterone receptor membrane component 1 and its role in ovarian follicle growth. Frontiers in neuroscience. 2013;7:99.
Wang Y, Feng H, Bi C, Zhu L, Pollard JW, Chen B. GSK-3β mediates in the progesterone inhibition of estrogen induced cyclin D2 nuclear localization and cell proliferation in cyclin D1−/− mouse uterine epithelium. FEBS letters. 2007;581(16):3069-75.
Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocrine reviews. 2014;35(6):851-905.
Inman JL, Robertson C, Mott JD, Bissell MJ. Mammary gland development: cell fate specification, stem cells and the microenvironment. Development. 2015;142(6):1028-42.
Brisken C. Progesterone signalling in breast cancer: a neglected hormone coming into the limelight. Nature Reviews Cancer. 2013;13(6):385-96.
Simpson ER. Sources of estrogen and their importance. The Journal of steroid biochemistry and molecular biology. 2003;86(3-5):225-30.
Davison SL, Davis SR. Androgens in women. The Journal of steroid biochemistry and molecular biology. 2003;85(2-5):363-6.
Burger HG. Androgen production in women. Fertility and sterility. 2002;77:3-5.
Ito K, Utsunomiya H, Suzuki T, Saitou S, Akahira J-I, Okamura K, et al. 17β-hydroxysteroid dehydrogenases in human endometrium and its disorders. Molecular and cellular endocrinology. 2006;248(1-2):136-40.
Dassen H, Punyadeera C, Kamps R, Delvoux B, Van Langendonckt A, Donnez J, et al. Estrogen metabolizing enzymes in endometrium and endometriosis. Human Reproduction. 2007;22(12):3148-58.
Labrie F, editor Adrenal androgens and intracrinology. Seminars in reproductive medicine; 2004: Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New ….
Bianchi VE, Bresciani E, Meanti R, Rizzi L, Omeljaniuk RJ, Torsello A. The role of androgens in women's health and wellbeing. Pharmacological research. 2021;171:105758.
Longcope C. 1 Adrenal and gonadal androgen secretion in normal females. Clinics in endocrinology and metabolism. 1986;15(2):213-28.
Davison SL, Bell R, Donath S, Montalto J, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. The Journal of Clinical Endocrinology & Metabolism. 2005;90(7):3847-53.
Couzinet B, Meduri G, Lecce MG, Young J, Brailly S, Loosfelt H, et al. The postmenopausal ovary is not a major androgen-producing gland. The Journal of Clinical Endocrinology & Metabolism. 2001;86(10):5060-6.
Taieb J, Mathian B, Millot F, Patricot M-C, Mathieu E, Queyrel N, et al. Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography–mass spectrometry in sera from 116 men, women, and children. Clinical chemistry. 2003;49(8):1381-95.
Walters K, Handelsman D. Role of androgens in the ovary. Molecular and cellular endocrinology. 2018;465:36-47.
Stárka L, Dušková M, Hill M. Dehydroepiandrosterone: a neuroactive steroid. The Journal of steroid biochemistry and molecular biology. 2015;145:254-60.
Lenie S, Smitz J. Functional AR signaling is evident in an in vitro mouse follicle culture bioassay that encompasses most stages of folliculogenesis. Biology of Reproduction. 2009;80(4):685-95.
McEwan IJ, McGuinness D, Hay CW, Millar RP, Saunders PT, Fraser HM. Identification of androgen receptor phosphorylation in the primate ovary in vivo. Reproduction (Cambridge, England). 2010;140(1):93.
Hampton J, Manikkam M, Lubahn D, Smith M, Garverick H. Androgen receptor mRNA expression in the bovine ovary. Domestic Animal Endocrinology. 2004;27(1):81-8.
Kimura S, Matsumoto T, Matsuyama R, Shiina H, Sato T, Takeyama K-i, et al. Androgen receptor function in folliculogenesis and its clinical implication in premature ovarian failure. Trends in Endocrinology & Metabolism. 2007;18(5):183-9.
Conforti A, Carbone L, Di Girolamo R, Iorio GG, Guida M, Campitiello MR, et al. Therapeutic management in women with a diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials. Fertility and Sterility. 2024.
Wang ET, Diamond MP, Alvero R, Casson P, Christman GM, Coutifaris C, et al. Androgenicity and fertility treatment in women with unexplained infertility. Fertility and sterility. 2020;113(3):636-41.
Magamage MP, Zengyo M, Moniruzzaman M, Miyano T. Testosterone induces activation of porcine primordial follicles in vitro. Reproductive Medicine and Biology. 2011;10:21-30.
Walters K, Paris VR, Aflatounian A, Handelsman DJ. Androgens and ovarian function: translation from basic discovery research to clinical impact. Journal of Endocrinology. 2019;242(2):R23-R50.
Simitsidellis I, Saunders PT, Gibson DA. Androgens and endometrium: new insights and new targets. Molecular and cellular endocrinology. 2018;465:48-60.
Mertens H, Heineman M-J, Theunissen P, De Jong F, Evers J. Androgen, estrogen and progesterone receptor expression in the human uterus during the menstrual cycle. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2001;98(1):58-65.
Ley SH, Li Y, Tobias DK, Manson JE, Rosner B, Hu FB, et al. Duration of reproductive life span, age at menarche, and age at menopause are associated with risk of cardiovascular disease in women. Journal of the American Heart Association. 2017;6(11):e006713.
Kische H, Gross S, Wallaschofski H, Grabe HJ, Völzke H, Nauck M, et al. Associations of androgens with depressive symptoms and cognitive status in the general population. PloS one. 2017;12(5):e0177272.
Notelovitz M. Androgen effects on bone and muscle. Fertil Steril. 2002 Apr;77 Suppl 4:S34-41. PubMed PMID: 12007900. Epub 2002/05/15. eng.
Referanslar
Lee MM. Reproductive hormones in infant girls—a harbinger of adult reproductive function? : Oxford University Press; 2003. p. 3513-4.
Sehested A, Juul A, Andersson AM, Petersen JH, Jensen TK, Müller J, et al. Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels. The Journal of Clinical Endocrinology & Metabolism. 2000;85(4):1634-40.
Hobeika E, Armouti M, Kala HS, Stocco C. Ovarian hormones. Hormonal Signaling in Biology and Medicine: Elsevier; 2020. p. 565-83.
Simpson ER, editor Models of aromatase insufficiency. Seminars in reproductive medicine; 2004: Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New ….
Segawa T, Teramoto S, Omi K, Miyauchi O, Watanabe Y, Osada H. Changes in estrone and estradiol levels during follicle development: a retrospective large-scale study. Reproductive Biology and Endocrinology. 2015;13:1-7.
Canipari R. Oocyte–granulosa cell interactions. Human reproduction update. 2000;6(3):279-89.
Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis—some new perspectives. Endocrinology. 2001;142(11):4589-94.
Stocco C. Aromatase expression in the ovary: hormonal and molecular regulation. Steroids. 2008;73(5):473-87.
Monget P, Bondy C. Importance of the IGF system in early folliculogenesis. Molecular and cellular endocrinology. 2000;163(1-2):89-93.
Richards JS. Perspective: the ovarian follicle—a perspective in 2001. Endocrinology. 2001;142(6):2184-93.
Britt K, Findlay J. Estrogen actions in the ovary revisited. Journal of Endocrinology. 2002;175(2):269-76.
Marino M, Galluzzo P, Ascenzi P. Estrogen signaling multiple pathways to impact gene transcription. Current genomics. 2006;7(8):497-508.
Prossnitz ER, Barton M. The G-protein-coupled estrogen receptor GPER in health and disease. Nature Reviews Endocrinology. 2011;7(12):715-26.
Otto C, Fuchs I, Kauselmann G, Kern H, Zevnik B, Andreasen P, et al. GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biology of reproduction. 2009;80(1):34-41.
Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Human reproduction update. 2014;20(4):485-500.
Wang H, Eriksson Hk, Sahlin L. Estrogen receptors α and β in the female reproductive tract of the rat during the estrous cycle. Biology of reproduction. 2000;63(5):1331-40.
Winuthayanon W, Bernhardt ML, Padilla-Banks E, Myers PH, Edin ML, Lih FB, et al. Oviductal estrogen receptor α signaling prevents protease-mediated embryo death. elife. 2015;4:e10453.
Orihuela PA, Croxatto HB. Acceleration of oviductal transport of oocytes induced by estradiol in cycling rats is mediated by nongenomic stimulation of protein phosphorylation in the oviduct. Biology of Reproduction. 2001;65(4):1238-45.
Zhu L, Pollard JW. Estradiol-17β regulates mouse uterine epithelial cell proliferation through insulin-like growth factor 1 signaling. Proceedings of the National Academy of Sciences. 2007;104(40):15847-51.
Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science. 2005;308(5728):1583-7.
Scarabin P-Y. Hormones and venous thromboembolism among postmenopausal women. Climacteric. 2014;17(sup2):34-7.
Syan SK, Minuzzi L, Costescu D, Smith M, Allega OR, Coote M, et al. Influence of endogenous estradiol, progesterone, allopregnanolone, and dehydroepiandrosterone sulfate on brain resting state functional connectivity across the menstrual cycle. Fertility and sterility. 2017;107(5):1246-55. e4.
Filicori M, Butler JP, Crowley W. Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion. The Journal of clinical investigation. 1984;73(6):1638-47.
Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocrine reviews. 2007;28(1):117-49.
Condon JC, Hardy DB, Kovaric K, Mendelson CR. Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-κB may contribute to the onset of labor through inhibition of PR function. Molecular endocrinology. 2006;20(4):764-75.
Garg D, Ng SSM, Baig KM, Driggers P, Segars J. Progesterone-mediated non-classical signaling. Trends in Endocrinology & Metabolism. 2017;28(9):656-68.
Devoto L, Vega M, Kohen P, Castro O, Carvallo P, Palomino A. Molecular regulation of progesterone secretion by the human corpus luteum throughout the menstrual cycle. Journal of reproductive immunology. 2002;55(1-2):11-20.
Duffy DM, Chaffin CL, Stouffer RL. Expression of estrogen receptor α and β in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone. Endocrinology. 2000;141(5):1711-7.
Peluso JJ. Progesterone receptor membrane component 1 and its role in ovarian follicle growth. Frontiers in neuroscience. 2013;7:99.
Wang Y, Feng H, Bi C, Zhu L, Pollard JW, Chen B. GSK-3β mediates in the progesterone inhibition of estrogen induced cyclin D2 nuclear localization and cell proliferation in cyclin D1−/− mouse uterine epithelium. FEBS letters. 2007;581(16):3069-75.
Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocrine reviews. 2014;35(6):851-905.
Inman JL, Robertson C, Mott JD, Bissell MJ. Mammary gland development: cell fate specification, stem cells and the microenvironment. Development. 2015;142(6):1028-42.
Brisken C. Progesterone signalling in breast cancer: a neglected hormone coming into the limelight. Nature Reviews Cancer. 2013;13(6):385-96.
Simpson ER. Sources of estrogen and their importance. The Journal of steroid biochemistry and molecular biology. 2003;86(3-5):225-30.
Davison SL, Davis SR. Androgens in women. The Journal of steroid biochemistry and molecular biology. 2003;85(2-5):363-6.
Burger HG. Androgen production in women. Fertility and sterility. 2002;77:3-5.
Ito K, Utsunomiya H, Suzuki T, Saitou S, Akahira J-I, Okamura K, et al. 17β-hydroxysteroid dehydrogenases in human endometrium and its disorders. Molecular and cellular endocrinology. 2006;248(1-2):136-40.
Dassen H, Punyadeera C, Kamps R, Delvoux B, Van Langendonckt A, Donnez J, et al. Estrogen metabolizing enzymes in endometrium and endometriosis. Human Reproduction. 2007;22(12):3148-58.
Labrie F, editor Adrenal androgens and intracrinology. Seminars in reproductive medicine; 2004: Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New ….
Bianchi VE, Bresciani E, Meanti R, Rizzi L, Omeljaniuk RJ, Torsello A. The role of androgens in women's health and wellbeing. Pharmacological research. 2021;171:105758.
Longcope C. 1 Adrenal and gonadal androgen secretion in normal females. Clinics in endocrinology and metabolism. 1986;15(2):213-28.
Davison SL, Bell R, Donath S, Montalto J, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. The Journal of Clinical Endocrinology & Metabolism. 2005;90(7):3847-53.
Couzinet B, Meduri G, Lecce MG, Young J, Brailly S, Loosfelt H, et al. The postmenopausal ovary is not a major androgen-producing gland. The Journal of Clinical Endocrinology & Metabolism. 2001;86(10):5060-6.
Taieb J, Mathian B, Millot F, Patricot M-C, Mathieu E, Queyrel N, et al. Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography–mass spectrometry in sera from 116 men, women, and children. Clinical chemistry. 2003;49(8):1381-95.
Walters K, Handelsman D. Role of androgens in the ovary. Molecular and cellular endocrinology. 2018;465:36-47.
Stárka L, Dušková M, Hill M. Dehydroepiandrosterone: a neuroactive steroid. The Journal of steroid biochemistry and molecular biology. 2015;145:254-60.
Lenie S, Smitz J. Functional AR signaling is evident in an in vitro mouse follicle culture bioassay that encompasses most stages of folliculogenesis. Biology of Reproduction. 2009;80(4):685-95.
McEwan IJ, McGuinness D, Hay CW, Millar RP, Saunders PT, Fraser HM. Identification of androgen receptor phosphorylation in the primate ovary in vivo. Reproduction (Cambridge, England). 2010;140(1):93.
Hampton J, Manikkam M, Lubahn D, Smith M, Garverick H. Androgen receptor mRNA expression in the bovine ovary. Domestic Animal Endocrinology. 2004;27(1):81-8.
Kimura S, Matsumoto T, Matsuyama R, Shiina H, Sato T, Takeyama K-i, et al. Androgen receptor function in folliculogenesis and its clinical implication in premature ovarian failure. Trends in Endocrinology & Metabolism. 2007;18(5):183-9.
Conforti A, Carbone L, Di Girolamo R, Iorio GG, Guida M, Campitiello MR, et al. Therapeutic management in women with a diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials. Fertility and Sterility. 2024.
Wang ET, Diamond MP, Alvero R, Casson P, Christman GM, Coutifaris C, et al. Androgenicity and fertility treatment in women with unexplained infertility. Fertility and sterility. 2020;113(3):636-41.
Magamage MP, Zengyo M, Moniruzzaman M, Miyano T. Testosterone induces activation of porcine primordial follicles in vitro. Reproductive Medicine and Biology. 2011;10:21-30.
Walters K, Paris VR, Aflatounian A, Handelsman DJ. Androgens and ovarian function: translation from basic discovery research to clinical impact. Journal of Endocrinology. 2019;242(2):R23-R50.
Simitsidellis I, Saunders PT, Gibson DA. Androgens and endometrium: new insights and new targets. Molecular and cellular endocrinology. 2018;465:48-60.
Mertens H, Heineman M-J, Theunissen P, De Jong F, Evers J. Androgen, estrogen and progesterone receptor expression in the human uterus during the menstrual cycle. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2001;98(1):58-65.
Ley SH, Li Y, Tobias DK, Manson JE, Rosner B, Hu FB, et al. Duration of reproductive life span, age at menarche, and age at menopause are associated with risk of cardiovascular disease in women. Journal of the American Heart Association. 2017;6(11):e006713.
Kische H, Gross S, Wallaschofski H, Grabe HJ, Völzke H, Nauck M, et al. Associations of androgens with depressive symptoms and cognitive status in the general population. PloS one. 2017;12(5):e0177272.
Notelovitz M. Androgen effects on bone and muscle. Fertil Steril. 2002 Apr;77 Suppl 4:S34-41. PubMed PMID: 12007900. Epub 2002/05/15. eng.
