Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-kw2vx Total loading time: 0 Render date: 2025-01-07T23:12:21.796Z Has data issue: false hasContentIssue false

Chapter 6 - The Role of Progesterone in Pregnancy

from Section I - Hormones in the Physiology and Pharmacology of Pregnancy

Published online by Cambridge University Press:  09 November 2022

By
Sam Mesiano
Edited by
Felice Petraglia ,
Mariarosaria Di Tommaso  and
Federico Mecacci
Felice Petraglia
Affiliation:
Università degli Studi, Florence
Mariarosaria Di Tommaso
Affiliation:
Università degli Studi, Florence
Federico Mecacci
Affiliation:
Università degli Studi, Florence
Get access

Summary

The steroid hormone progesterone (P4: 4-pregnene-3,20-dione), acting via nuclear P4 receptors (PRs), is a major regulator of the female reproductive system. P4 produced by the ovarian corpus luteum (CL) acts on uterine endometrial cells to create a tissue and intrauterine environment conducive for embryo implantation and the establishment of pregnancy. Aptly referred to as the hormone of pregnancy, P4 is essential for the establishment and maintenance of pregnancy, and the physiologic control of its withdrawal is the principal trigger for parturition. This chapter examines the evolutionary biology and past and recent advances in research to elucidate the mechanism of action and regulation of P4/PR signaling in the hormonal control of pregnancy and parturition. Exploiting this pathway may be a key to clinically controlling the onset of labor and preventing pre-term birth.

Type
Chapter
Information
Hormones and Pregnancy
Basic Science and Clinical Implications
 , pp. 50 - 60
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Callard, IP, Fileti, LA, Perez, LE, et al. Role of the corpus luteum and progesterone in the evolution of vertebrate viviparity. Am. Zool. 1992, 32:264–275.Google Scholar
Hisaw, FL. Endocrine adaptations of the mammalian estrous cycle and gestation. In: Gorbman, A, ed. Comparative Endocrinology. 1959; 533–552. New York.: John Wiley & Sons.Google Scholar
Wilson, SC, andSharp, PJ. The effects of progesterone on oviposition and ovulation in the domestic fowl (Gallus domesticus). Br Poult Sci. 1976, 17:163–173.CrossRefGoogle ScholarPubMed
Thornton, JW. Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc Natl Acad Sci USA. 2001, 98:5671–5676.Google Scholar
Corner, GW. The Hormones in Human Reproduction. London: Princeton University Press.Google Scholar
Allen, WM. Recollections of my life with progesterone. Gynecol Invest. 1974, 5:142–182.Google Scholar
Corner, GW, Sr. The early history of progesterone. Gynecol Invest. 1974, 5:106–112.CrossRefGoogle ScholarPubMed
Medvei, VC. A History of Clinical Endocrinology. New York: The Parthenon Publishing Group.Google Scholar
Frobenius, W. Ludwig Fraenkel: ‘Spiritus rector’ of the early progesterone research. Eur J Obstet Gynecol Reprod Biol. 1999, 83:115–119.Google Scholar
Allen, WM, and Wintersteiner, O. Crystalline progestin. Science. 1934, 80:190–191.CrossRefGoogle ScholarPubMed
Butenandt, A, andWestphal, U. Zur Isolierung und Characterisierung des Corpus-luteum-Hormons. Ber Chem Ges. 1934, 67:1440–1442.Google Scholar
Hartmann, M, and Wettstein, A. Ein krystallisiertes Hormon aus Corpus luteum. Helv Chim Acta. 1934, 17:878–882.CrossRefGoogle Scholar
Slotta, K, Ruschig, H, and Fels, E. Reindarstellung der Hormone aus dem Corpus luteum. Ber Chem Ges. 1934, 67:1270–1273.CrossRefGoogle Scholar
Allen, WM, Butenandt, A, Corner, GW, et al. Nomenclature of corpus luteum hormone. Science. 1935, 82:153.Google Scholar
Davis, ME, and Wied, GL. 17-alpha-hydroxyprogesterone-caproate: A new substance with prolonged progestational activity: A comparison with chemically pure progesterone. J Clin Endocrinol Metabol. 1955, 15:923–930.CrossRefGoogle ScholarPubMed
Venning, EH, and Browne, JSL. Isolation of a water-soluble pregnandiol complex from human pregnancy urine. Proc Soc Exper Biol and Med. 1936, 34:729.Google Scholar
Venning, EH. Gravimetric method for the determination of sodium pregnandiol glucuronidate (an excretion product of progesterone). J Biol Chem. 1937, 119:473.CrossRefGoogle Scholar
Wilson, KM, and Rochester, NY. Pregnancy complicated by ovarian and paraovarian tumors. Am J Ob/Gyn. 1937, 34:977–986.Google Scholar
Csapo, AI, Pulkkinen, MO, Ruttner, B, et al. The significance of the human corpus luteum in pregnancy maintenance. I. Preliminary studies. Am J Obstet Gynecol. 1972, 112:1061–1067.Google Scholar
Csapo, A. The luteo-placental shift, the guardian of pre-natal life. Postgrad Med J. 1969, 45:57–64.Google Scholar
O’Malley, BW. In vitro hormonal induction of a specific protein (avidin) in chick oviduct. Biochemistry. 1967, 6:2546–2551.Google Scholar
O’Malley, BW, and Korenman, SG. Studies on the mechanism of hormone induction of a specific protein. Immunological identity and kinetic studies of avidin synthesized in vitro by the chick oviduct. Life Sci. 1967, 6:1953–1959.Google Scholar
Milgrom, E, Atger, M, and Baulieu, EE. Progesterone in uterus and plasma. IV. Progesterone receptor(s) in guinea pig uterus cytosol. Steroids. 1970, 16:741–754.Google Scholar
Smith, RG, Iramain, CA, Buttram, VC, Jr., et al. Purification of human uterine progesterone receptor. Nature. 1975, 253:271–272.Google Scholar
Heikinheimo, O, Kontula, K, Croxatto, H, et al. Plasma concentrations and receptor binding of RU 486 and its metabolites in humans. J Steroid Biochem. 1987, 26:279–284.Google Scholar
Gellersen, B, Brosens, IA, and Brosens, JJ. Decidualization of the human endometrium: mechanisms, functions, and clinical perspectives. Sem Reprod Med. 2007, 25:445–453.Google Scholar
Mao, G, Wang, J, Kang, Y, et al. Progesterone increases systemic and local uterine proportions of CD4+CD25+ Treg cells during midterm pregnancy in mice. Endocrinology. 2010, 151:5477–5488.Google Scholar
Renthal, NE, Chen, CC, Williams, KC, et al. miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc Natl Acad Sci USA. 2010, 107:20828–20833.Google Scholar
Siiteri, PK, Febres, F, Clemens, LE, et al. Progesterone and maintenance of pregnancy: is progesterone nature’s immunosuppressant? Ann NY Acad Sci. 1977, 286:384–397.Google Scholar
Hardy, DB, Janowski, BA, Corey, DR, et al. Progesterone receptor plays a major antiinflammatory role in human myometrial cells by antagonism of nuclear factor-kappaB activation of cyclooxygenase 2 expression. Mol Endocrinol. 2006, 20:2724–2733.Google Scholar
Thomson, AJ, Telfer, JF, Young, A, et al. Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process. Hum Reproduct. 1999, 14:229–236.Google Scholar
Osman, I, Young, A, Jordan, F, et al. Leukocyte density and proinflammatory mediator expression in regional human fetal membranes and decidua before and during labor at term. J Soc Gynecol Invest. 2006, 13:97–103.CrossRefGoogle ScholarPubMed
Mesiano, S, Chan, EC, Fitter, JT, et al. Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium. J Clin Endocrinol Metabol. 2002, 87:2924–2930.Google Scholar
Tan, H, Yi, L, Rote, NS, et al. Progesterone receptor-A and -B have opposite effects on proinflammatory gene expression in human myometrial cells: Implications for progesterone actions in human pregnancy and parturition. J Clin Endocrinol Metabol. 2012, 97:E719–730.Google Scholar
Merlino, AA, Welsh, TN, Tan, H, et al. Nuclear progesterone receptors in the human pregnancy myometrium: evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A. J Clin Endocrinol Metabol. 2007, 92:1927–1933.Google Scholar
Chai, SY, Smith, R, Fitter, JT, et al. Increased progesterone receptor A expression in labouring human myometrium is associated with decreased promoter occupancy by the histone demethylase JARID1A. Mol Hum Reprod. 2014, 20:442–453.CrossRefGoogle ScholarPubMed
Amini, P, Michniuk, D, Kuo, K, et al. Human parturition involves phosphorylation of progesterone receptor-A at serine-345 in myometrial cells. Endocrinology. 2016, 157:4434–4445.Google Scholar
Condon, JC, Jeyasuria, P, Faust, JM, et al. A decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition. Proc Natl Acad Sci USA. 2003, 100:9518–9523.Google Scholar
Mahendroo, MS, Porter, A, Russell, DW, et al. The parturition defect in steroid 5alpha-reductase type 1 knockout mice is due to impaired cervical ripening. Mol Endocrinol. 1999, 13:981–992.Google ScholarPubMed
Nadeem, L, Shynlova, O, Matysiak-Zablocki, E, et al. Molecular evidence of functional progesterone withdrawal in human myometrium. Nat Commun. 2016, 7:11565.Google Scholar
Nadeem, L, Shynlova, O, Mesiano, S, et al. Progesterone via its type-A receptor promotes myometrial gap junction coupling. Sci Rep. 2017, 7:13357.Google Scholar
Bengtsson, LP. The Effect of Progesterone on the Maintenance of Early Pregnancy. Paper presented at: Brook Lodge Symposium: Progesterone 1961; Augusta, MI.Google Scholar
Pinto, RM, Montuori, E, Lerner, U, et al. Effect of progesterone on the oxytocic action of estradiol-17-beta. Am J Obstet Gynecol. 1965, 91:1084–1089.Google Scholar
Keirse, MJ. Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynaecol. 1990, 97:149–154.Google Scholar
da Fonseca, EB, Bittar, RE, Carvalho, MH, et al. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003, 188:419–424.Google Scholar
Meis, PJ, Klebanoff, M, Thom, E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003, 348:2379–2385.Google Scholar
Norman, JE, Marlow, N, Messow, CM, et al. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): A multicentre, randomised, double-blind trial. Lancet. 2016, 387:2106–2116.Google Scholar
Blackwell, SC, Gyamfi-Bannerman, C, Biggio, JR, Jr., et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG Study): A multicenter, international. Randomized Double-Blind Trial. Am J Perinatol. 2020, 37:127–136.Google ScholarPubMed
Weatherborn, M, and Mesiano, S. Rationale for current and future progestin-based therapies to prevent preterm birth. Best Prac Res Clin Obstet Gynaecol. 2018, 52:114–125.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×