20 alpha dihydroprogesterone


Summary: A biologically active 20-alpha-reduced metabolite of PROGESTERONE. It is converted from progesterone to 20-alpha-hydroxypregn-4-en-3-one by the 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE in the CORPUS LUTEUM and the PLACENTA.

Top Publications

  1. Petrino T, Lin Y, Wallace R. Steroidogenesis in Fundulus heteroclitus. I. Production of 17 alpha-hydroxy,20 beta-dihydroprogesterone, testosterone, and 17 beta-estradiol by prematurational follicles in vitro. Gen Comp Endocrinol. 1989;73:147-56 pubmed
  2. Petrino T, Greeley M, Selman K, Lin Y, Wallace R. Steroidogenesis in Fundulus heteroclitus. II. Production of 17 alpha-hydroxy-20 beta-dihydroprogesterone, testosterone, and 17 beta-estradiol by various components of the ovarian follicle. Gen Comp Endocrinol. 1989;76:230-40 pubmed
  3. Daniel S, Armstrong D, Gore Langton R. Growth and development of rat oocytes in vitro. Gamete Res. 1989;24:109-21 pubmed
    ..6% and 47.1% of penetrated oocytes with development of these apparently normal zygotes to two-cell embryos being 66.7% and 62.5%, respectively. ..
  4. Wiebe J, De Gannes G, Dallaire M. Synthesis of the allylic regulatory steroid, 3 alpha-hydroxy-4-pregnen-20-one, by rat granulosa cells and its regulation by gonadotropins. Biol Reprod. 1994;50:956-64 pubmed
    ..abstract truncated at 250 words) ..
  5. McMillen I, Jenkin G, Haji Baba A, Browne C, Thorburn G. Effect of gamma 3 or gamma 2 melanocyte stimulating hormone on steroidogenesis in the fetal sheep during late gestation. Life Sci. 1989;44:563-9 pubmed
  6. Kamernitskii A, Levina I. [Pregna-D'-pentaranes, progestins, and antiprogestins: II. Pathways and realization mechanisms of separate biological functions of steroid hormones]. Bioorg Khim. 2005;31:227-38 pubmed
    ..The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru. ..
  7. Matsuda J, Noda K, Shiota K, Takahashi M. Participation of ovarian 20 alpha-hydroxysteroid dehydrogenase in luteotrophic and luteolytic processes during rat pseudopregnancy. J Reprod Fertil. 1990;88:467-74 pubmed
    ..abstract truncated at 250 words) ..
  8. Frye C, Paris J, Rhodes M. Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5alpha-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex. Reproduction. 2007;133:663-74 pubmed
    ..Thus, paced mating enhances concentrations of 5alpha-reduced progestins in brain areas associated with reproduction (midbrain), as well as exploration/anxiety (hippocampus and striatum) and social behavior (cortex). ..
  9. Oh S, Yedidag E, Bielefeldt K. Differential effects of progesterone and its analogues on the contractility of the murine jejunum in vitro. J Surg Res. 1998;75:1-5 pubmed
    ..Rather, they suggest a specific interaction between the steroid hormone and a still unidentified protein that differs in its function and pharmacological profile from the known progesterone receptor. ..

More Information


  1. Kiya T, Endo T, Henmi H, Goto T, Kitajima Y, Manase K, et al. The effects of growth hormone on corpus luteum of superovulated rats. Endocr Res. 1999;25:179-93 pubmed
    ..There are thought to be two mechanisms of GH-induced structural luteolysis. One is apoptosis, and the other is destruction of extracellular matrix by MMP. ..
  2. McKenna S, Simon N. Genetic differences in progestin sensitivity in CD-1 and SW female mice. Physiol Behav. 1993;54:167-70 pubmed
    ..The potential mechanisms mediating genotype-based differences in responsiveness are discussed, and the relationship of this report to previously described strain differences in progestin sensitivity are considered. ..
  3. Higashi T, Nagahama A, Mukai Y, Shimada K. Studies on neurosteroids XXII. Liquid chromatography-tandem mass spectrometric method for profiling rat brain 3-oxo-4-ene-neuroactive steroids. Biomed Chromatogr. 2008;22:34-43 pubmed
    ..The limits of quantitation were 0.1 ng/g tissue for all the steroids. The application of this developed method for the analysis of changes in the brain neuroactive steroid levels by immobilization stress is also presented. ..
  4. Choi J, Ishida M, Matsuwaki T, Yamanouchi K, Nishihara M. Involvement of 20alpha-hydroxysteroid dehydrogenase in the maintenance of pregnancy in mice. J Reprod Dev. 2008;54:408-12 pubmed
    ..These results suggest that both maternal and fetal 20alpha-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses. ..
  5. Astle S, Khan R, Thornton S. The effects of a progesterone metabolite, 5 beta-dihydroprogesterone, on oxytocin receptor binding in human myometrial membranes. BJOG. 2003;110:589-92 pubmed
    ..We conclude that 5 beta-dihydroprogesterone is unlikely to regulate myometrial activity as a result of a direct effect on oxytocin receptor binding or inward calcium current. ..
  6. Fisch B, Margara R, Winston R, Hillier S. Cellular basis of luteal steroidogenesis in the human ovary. J Endocrinol. 1989;122:303-11 pubmed
    ..The culture system described should be of value in further defining the control of human CL form and function at the cellular level. ..
  7. de Lignieres B, Dennerstein L, Backstrom T. Influence of route of administration on progesterone metabolism. Maturitas. 1995;21:251-7 pubmed
    ..The known psychotropic effects of 5 alpha- and 5 beta-pregnanolone lead to different indications and precautions for oral and vaginal administration of progesterone. ..
  8. Roby K, Terranova P. Effects of tumor necrosis factor-alpha in vitro on steroidogenesis of healthy and atretic follicles of the rat: theca as a target. Endocrinology. 1990;126:2711-8 pubmed
    ..The data imply that TNF has differential effects on thecal and granulosa steroidogenesis. ..
  9. Saragueta P, Krimer A, Charreau E, Tesone M. Insulin regulation of steroidogenic activity in rat culture luteal cells. J Steroid Biochem. 1989;32:393-7 pubmed
    ..These data suggest that luteal cell function is regulated by insulin and that this hormone has a direct effect on the steroidogenic process. ..
  10. Lin S, Han Q, Azzi A, Zhu D, Gangloff A, Campbell R, et al. 3D-structure of human estrogenic 17beta-HSD1: binding with various steroids. J Steroid Biochem Mol Biol. 1999;69:425-9 pubmed
    ..These results give evidence for the structural basis of steroid recognition by 17beta-HSD1 and throw light on the design of new inhibitors for this pivotal steroid enzyme. ..
  11. Sawada T, Hou M, Tamada H, Mori J. Secretion of progesterone and 20 alpha-dihydroprogesterone during the estrous cycle in goats. Steroids. 1994;59:672-5 pubmed
    ..These results indicate that in the goat after estrus, there is much 20 alpha-DHP in the peripheral plasma. Progesterone may be catabolized to the biologically inactive steroid, 20 alpha-DHP, during luteolysis. ..
  12. Suh B, Sprengel R, Keren Tal I, Himmelhoch S, Amsterdam A. Introduction of a gonadotropin receptor expression plasmid into immortalized granulosa cells leads to reconstitution of hormone-dependent steroidogenesis. J Cell Biol. 1992;119:439-50 pubmed
  13. Fanjul L, Estevez F, Déniz Cáceres A, Marrero I, Benitez L, Centol I, et al. The androgen receptor does not mediate progestin regulation of progesterone biosynthesis in cultured rat granulosa cells. Biochem Int. 1989;19:977-84 pubmed
  14. Stein P, Bussmann L, Tesone M. In vivo regulation of the steroidogenic activity of rat luteal cells by insulin. J Steroid Biochem Mol Biol. 1995;52:329-35 pubmed
    ..001) with a concomitantly diminished LH responsiveness. It is concluded that in vivo treatment of superovulated rats with insulin increases luteal progestagen production by increasing the content of cytochrome P450scc. ..
  15. Steimer T, Driscoll P, Schulz P. Brain metabolism of progesterone, coping behaviour and emotional reactivity in male rats from two psychogenetically selected lines. J Neuroendocrinol. 1997;9:169-75 pubmed
  16. Mahendroo M, Porter A, Russell D, Word R. The parturition defect in steroid 5alpha-reductase type 1 knockout mice is due to impaired cervical ripening. Mol Endocrinol. 1999;13:981-92 pubmed
  17. Mathias S, Wei L, Hunter E, Wells O, Mgbonyebi O, Mrotek J. Optimizing ACTH-stimulated steroid secretion by cultured adrenocortical tumor cells. Endocr Res. 1995;21:121-7 pubmed
  18. Quinkler M, Johanssen S, Bumke Vogt C, Oelkers W, Bahr V, Diederich S. Enzyme-mediated protection of the mineralocorticoid receptor against progesterone in the human kidney. Mol Cell Endocrinol. 2001;171:21-4 pubmed
    ..These results confirm the existence of an efficient renal enzyme system as a possible mechanism of an enzyme-mediated MC receptor selectivity. ..
  19. Wiebe J, Kavaliers M. Analgesic effects of the putative FSH-suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one: possible modes of action. Brain Res. 1988;461:150-7 pubmed
    ..These findings also suggest possible central modes of action whereby 3A4P may elicit selective suppression of FSH. ..
  20. Pellicer A, Miro F. Steroidogenesis in vitro of human granulosa-luteal cells pretreated in vivo with gonadotropin-releasing hormone analogs. Fertil Steril. 1990;54:590-6 pubmed
    ..It seems that, at least in part, this change is due to the stimulation of the metabolizing enzyme 20 alpha-hydroxysteroid dehydrogenase by GnRH-a. ..
  21. Nieuwenhuizen A, Schuiling G, Liem S, Moes H, Koiter T, Uilenbroek J. Progesterone stimulates pancreatic cell proliferation in vivo. Eur J Endocrinol. 1999;140:256-63 pubmed
    ..v. glucose load (0.5 g/kg body weight). It is concluded that progesterone stimulates pancreatic cell proliferation indirectly; gonadal factor(s), not identical to oestradiol, is (are) probably involved. ..
  22. Mills T, Stopper V. The use of perfused rabbit ovaries to investigate regional ovarian lymphatic flow. Lymphology. 1991;24:32-9 pubmed
    ..The flow of ovarian lymph and the output of progesterone and 20 alpha dihydroprogesterone in lymph and venous effluent from perfused ovaries were measured and the results compared to the same ..
  23. Bjurulf E, Selstam G, Olofsson J. Increased LH receptor mRNA and extended corpus luteum function induced by prolactin and indomethacin treatment in vivo in hysterectomized pseudopregnant rats. J Reprod Fertil. 1994;102:139-45 pubmed
    ..Furthermore, prolactin can sustain corpus luteum function by exerting a luteotrophic effect during the late luteal phase, as judged by the stimulation of progesterone synthesis and the expression of LH receptors. ..
  24. Melcangi R, Maggi R, Martini L. Testosterone and progesterone metabolism in the human neuroblastoma cell line SH-SY5Y. J Steroid Biochem Mol Biol. 1993;46:811-8 pubmed
    ..It is suggested that the SH-SY5Y cell line may represent a useful "in vitro" model for the study of the mechanisms involved in the control of androgen and P metabolism in nervous cells. ..
  25. Pau C, Pau K, Berria M, Spies H. Ovarian influence on gonadotropin and prolactin release in mated rabbits. Endocrine. 2000;13:25-35 pubmed
    ..Moreover, the presented observation that activin stimulates hypothalamic gonadotropin-releasing hormone (GnRH) release suggests a possible involvement of ovarian proteins in the production of a full-scale coitus-induced GnRH/LH surge. ..
  26. Melcangi R, Magnaghi V, Cavarretta I, Martini L, Piva F. Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives. Neuroscience. 1998;85:569-78 pubmed
  27. Wiebe J, Dhanvantari S, Watson P, Huang Y. Suppression in gonadotropes of gonadotropin-releasing hormone-stimulated follicle-stimulating hormone release by the gonadal- and neurosteroid 3 alpha-hydroxy-4-pregnen-20-one involves cytosolic calcium. Endocrinology. 1994;134:377-82 pubmed
    ..The consistent decrease in total FSH (released plus cellular content) by 3 alpha HP suggests that this neurosteroid may also suppress FSH synthesis. ..
  28. Komorowski J, Tsang B. Divergent effects of 1-oleoyl-2-acetylglycerol and tumor-promoting phorbol ester on rat granulosa cell steroidogenesis in vitro. Biol Reprod. 1990;43:73-9 pubmed
    ..Accumulation of P5 throughout the culture periods (1-24 h) was markedly increased by DG (20 micrograms/ml) but significantly inhibited in the presence of TPA (40 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  29. Uzunov D, Cooper T, Costa E, Guidotti A. Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography. Proc Natl Acad Sci U S A. 1996;93:12599-604 pubmed
    ..A fluoxetine stimulation of brain 3 alpha, 5 alpha-TH PROG biosynthesis might be operative in the anxiolytic and antidysphoric actions of this drug. ..
  30. Frye C, Walf A, Paris J. Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation of 5alpha-reduced progestogens and reduces anxiety-like behavior of middle-aged rats. Behav Pharmacol. 2010;21:530-9 pubmed publisher
    ..Therefore, effects of CEE to reduce anxiety-like behavior of middle-aged rats may be owing, in part, to its capacity to enhance levels of 3alpha,5alpha-THP in the hippocampus. ..
  31. Nahoul K, Gilbert M. Plasma C-21 steroids in conscious pregnant and non-pregnant rabbits with chronic catheterization of the femoral artery and the portal and hepatic veins. J Steroid Biochem Mol Biol. 1991;38:753-8 pubmed
    ..Thus, the ratio of F/B in the femoral artery was markedly increased in the pregnant animals; this ratio ranged from 0.20 to 1.12 in the non-pregnant group, and from 1.3 to 12.5 in the pregnant group. ..
  32. Sawada T, Nakatani T, Tamada H, Mori J. Secretion of progesterone and 20 alpha-dihydroprogesterone during pregnancy in goats. Steroids. 1994;59:468-71 pubmed
  33. Kavaliers M, Wiebe J, Galea L. Male preference for the odors of estrous female mice is enhanced by the neurosteroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP). Brain Res. 1994;646:140-4 pubmed
    ..These results suggest that the neurosteroid 3 alpha HP has facilitatory effects on olfactory mediated male sexual interest or motivation that involve interactions with the GABAA receptor. ..
  34. Chien E, Liao C, Chang C, Pu H, Lu L, Shie M, et al. The non-genomic effects on Na+/H+-exchange 1 by progesterone and 20alpha-hydroxyprogesterone in human T cells. J Cell Physiol. 2007;211:544-50 pubmed
  35. Bellemare V, Labrie F, Luu The V. Isolation and characterization of a cDNA encoding mouse 3alpha-hydroxysteroid dehydrogenase: an androgen-inactivating enzyme selectively expressed in female tissues. J Steroid Biochem Mol Biol. 2006;98:18-24 pubmed
    ..This role could be related to the inactivation of excess of androgen and progesterone that are more severely regulated than in man. ..
  36. Yoshida S, Shiota K, Nishihara M, Takahashi M. A novel steroid inhibitor for a rat 20alpha-hydroxysteroid dehydrogenase isozyme. Biol Reprod. 1997;57:1433-7 pubmed
  37. Barkan D, Jia H, Dantes A, Vardimon L, Amsterdam A, Rubinstein M. Leptin modulates the glucocorticoid-induced ovarian steroidogenesis. Endocrinology. 1999;140:1731-8 pubmed
    ..A direct action of leptin on the ovary is an additional element of a regulatory network that maintains the homeostasis of steroid production. ..
  38. Nowak F. Distribution and metabolism of 20 alpha-hydroxylated progestins in the female rat. J Steroid Biochem Mol Biol. 2002;80:469-79 pubmed
  39. Saito S, Matsuyama S, Shiota K, Takahashi M. Involvement of splenocytes in the control of corpus luteum function in the rat. Endocrinol Jpn. 1988;35:891-8 pubmed
    ..All of these phenomena were normalized by injecting the animals with splenocytes. Taken together with our previous findings, these results indicate that splenocytes are involved in the control of ovarian function. ..
  40. Zhang L, Chao R. [Determination of progesterone and its main metabolite in rat plasma and uterus using HPLC]. Yao Xue Xue Bao. 2004;39:613-7 pubmed
    ..2 +/- 1.11) h. 20alpha-OHP showed a similar Tmax with P. The method is accurate and convenient. It can be used to determine P and its main metabolite 20alpha-OHP simultaneously for studying their preclinical pharmacokinetics. ..
  41. Matsuyama S, Shiota K, Takahashi M. Possible role of transforming growth factor-beta as a mediator of luteotropic action of prolactin in rat luteal cell cultures. Endocrinology. 1990;127:1561-7 pubmed
  42. Maayan R, Fisch B, Galdor M, Kaplan B, Shinnar N, Kinor N, et al. Influence of 17beta-estradiol on the synthesis of reduced neurosteroids in the brain (in vivo) and in glioma cells (in vitro): possible relevance to mental disorders in women. Brain Res. 2004;1020:167-72 pubmed
    ..This process may be relevant to psychopathological disorders that are ascribed to drastic alterations in estrogen levels, such as premenstrual syndrome, pregnancy-related mental disorders, and postpartum "blues". ..
  43. Hughes F, Pringle C, Gorospe W. Production of progestin-stimulatory factor(s) by enriched populations of rat T and B lymphocytes. Biol Reprod. 1991;44:922-6 pubmed
    ..Media were removed and progesterone, 20 alpha-OH-P, and estrogen levels were quantified by RIA.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  44. Takagi K. [Effects of prostaglandin F2 alpha on steroidogenesis of the PMSG-hCG primed rat ovary in luteolysis]. Nihon Naibunpi Gakkai Zasshi. 1988;64:1024-37 pubmed
    ..Plasma progesterone (P4), plasma 20 alpha dihydroprogesterone (20 alpha OHP4), in vitro production of pregnenolone (P5) from endogenous cholesterol in ovarian ..
  45. Li Y, Kasson B. Androgens augment vasoactive intestinal peptide- and growth hormone-releasing hormone-stimulated progestin production by rat granulosa cells. Endocrinology. 1993;132:584-90 pubmed
    ..These studies demonstrate that androgens, but not estrogens, progestins, or glucocorticoids, augment VIP- and GH-releasing hormone-stimulated progestin production by cultured rat granulosa cells. ..
  46. Kehoe P, Mallinson K, McCormick C, Frye C. Central allopregnanolone is increased in rat pups in response to repeated, short episodes of neonatal isolation. Brain Res Dev Brain Res. 2000;124:133-6 pubmed
    ..Thus, the biosocial stress of isolation in neonatal rats alters central pregnane steroids. ..
  47. Veiga S, Leonelli E, Beelke M, Garcia Segura L, Melcangi R. Neuroactive steroids prevent peripheral myelin alterations induced by diabetes. Neurosci Lett. 2006;402:150-3 pubmed
    ..These results suggest that neuroactive steroids such as progesterone and dihydroprogesterone may represent therapeutic alternatives to counteract peripheral myelin alterations induced by diabetes. ..
  48. Saito H, Kaba H, Sato T, Kondo M, Takeshima Y, Edashige N, et al. Influence of electrical stimulation of the hypothalamus on ovarian steroidogenesis in hypophysectomized and adrenalectomized rats. Exp Clin Endocrinol. 1990;95:259-61 pubmed
    ..From these results, it might be suggested that these hypothalamic structures were involved in the regulation of ovarian steroidogenesis without participation of the pituitary and adrenal. ..
  49. Tsumagari S, Kamata J, Takagi K, Tanemura K, Yosai A, Takeishi M. 3 beta-Hydroxysteroid dehydrogenase activity and gestagen concentrations in bovine cotyledons and caruncles during gestation and parturition. J Reprod Fertil. 1994;102:35-9 pubmed
  50. Vanluchene E, Hinting A, Dhont M, Serreyn R, Vandekerckhove D. Steroid determinations in human ovarian follicular fluid using capillary gas chromatography. J Steroid Biochem. 1990;35:83-9 pubmed
    ..Apart from the "profiles" of unconjugated steroids, a semi-quantitative analysis of steroid conjugates is possible if a preliminary group separation with disposable anion exchanger columns is included. ..
  51. Roglio I, Bianchi R, Gotti S, Scurati S, Giatti S, Pesaresi M, et al. Neuroprotective effects of dihydroprogesterone and progesterone in an experimental model of nerve crush injury. Neuroscience. 2008;155:673-85 pubmed publisher
    ..Altogether, these observations suggest that DHP and P (i.e. two neuroactive steroids interacting with progesterone receptor) may be considered protective agents in case of nerve crush injury. ..
  52. Devoto L, Vega M, Castro O, Kohen P. Effect of the aromatase inhibitor 4-hydroxyandrostene-3,17-dione progesterone synthesis by human luteal cells. Fertil Steril. 1991;55:922-6 pubmed
    ..These data indicate that the actions of 4-OHA on P or E2 formation have different inhibitory mechanisms. ..
  53. Melcangi R, Cavarretta I, Magnaghi V, Ballabio M, Martini L, Motta M. Crosstalk between normal and tumoral brain cells. Effect on sex steroid metabolism. Endocrine. 1998;8:65-71 pubmed
    ..Work is presently in progress to identify the principle(s) responsible respectively for the activating and inhibiting actions here described. ..