Formation of Progesterone and Pregnenolone From [4-14c]cholesterol by the Intact Mid-Term Human Foeto—placental Unit Perfused in Vitro

Dt, Baird; Cockburn, F.; Galbraith, Alan; Rw, Kelly; Livingstone, J. R. B.

doi:10.1677/joe.0.0560187

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…With advancing gestational age, maternal serum-derived cholesterol replaces endogenously produced cholesterol as the major substrate of placental progesterone production in humans and baboons ( Baird et al, 1973 ; Babischkin et al, 1997a , b ; Henson, 1998 ; Shi et al, 1999 ). Addition of LDL to primary trophoblast cultures drastically suppresses de novo cholesterol synthesis, stimulates progesterone production and inhibits cholesteryl ester-forming ACAT ( Winkel et al, 1980a , b , 1981 ).…”

Section: Cholesterolmentioning

confidence: 99%

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

2018

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The steroid hormones progestagens, estrogens, androgens, and glucocorticoids as well as their precursor cholesterol are required for successful establishment and maintenance of pregnancy and proper development of the fetus. The human placenta forms at the interface of maternal and fetal circulation. It participates in biosynthesis and metabolism of steroids as well as their regulated exchange between maternal and fetal compartment. This review outlines the mechanisms of human placental handling of steroid compounds. Cholesterol is transported from mother to offspring involving lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SRB1) as well as ATP-binding cassette (ABC)-transporters, ABCA1 and ABCG1. Additionally, cholesterol is also a precursor for placental progesterone and estrogen synthesis. Hormone synthesis is predominantly performed by members of the cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 and hydroxysteroid dehydrogenases (HSDs) such as 3β-HSD and 17β-HSD. Placental estrogen synthesis requires delivery of sulfate-conjugated precursor molecules from fetal and maternal serum. Placental uptake of these precursors is mediated by members of the solute carrier (SLC) family including sodium-dependent organic anion transporter (SOAT), organic anion transporter 4 (OAT4), and organic anion transporting polypeptide 2B1 (OATP2B1). Maternal–fetal glucocorticoid transport has to be tightly regulated in order to ensure healthy fetal growth and development. For that purpose, the placenta expresses the enzymes 11β-HSD 1 and 2 as well as the transporter ABCB1. This article also summarizes the impact of diverse compounds and diseases on the expression level and activity of the involved transporters, receptors, and metabolizing enzymes and concludes that the regulatory mechanisms changing the physiological to a pathophysiological state are barely explored. The structure and the cellular composition of the human placental barrier are introduced. While steroid production, metabolism and transport in the placental syncytiotrophoblast have been explored for decades, few information is available for the role of placental-fetal endothelial cells in these processes. With regard to placental structure and function, significant differences exist between species. To further decipher physiologic pathways and their pathologic alterations in placental steroid handling, proper model systems are mandatory.

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Section: Cholesterolmentioning

confidence: 99%

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

2018

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“…However, it is doubtful whether hCG exerts a stimulatory effect on steroidogenesis in the human placenta [17,18]. On the other hand, Rosenberg and Bhatnagar [19] dem onstrated that hCG stimulates secretion of (decidual) pro lactin.…”

Section: Influence O F Human Prolactin On De Novo Synthesis O F Hcgmentioning

confidence: 99%

Effects of Prolactin on Secretion and Synthesis of Human Chorionic Gonadotropin in Human Term Placentas in vitro: Short-Term Increase in Secretion, Followed by Medium-Term Suppression of Synthesis and Secretion

Würfel

Beckmann

Austin

et al. 1992

Gynecol Obstet Invest

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We studied the influence of human prolactin on the secretion and de novo synthesis of human chorionic gonadotropin (hCG) in the human term placenta in culture. Placental tissue from 14 patients with uncomplicated pregnancies and deliveries was prepared mechanically, with addition of a Percoll gradient step. hCG levels were determined in the culture media and in the cytosolic fraction of cells by means of an enzyme immunoassay with coated beads. The amount of newly synthesized hCG was measured by the extent of incorporation of ³⁵S-methionine into the hCG molecule. Our results showed that human prolactin had two different effects in vitro: between ½ and 1 h, prolactin slightly increased secretion of hCG into the culture medium without affecting de novo synthesis; after 2 h, prolactin began to cause a significant decrease in both secretion and de novo synthesis of hCG over several hours. It appears that both effects are receptor mediated, for ovine prolactin failed to produce any response. We conclude that prolactin is one of the main factors regulating the synthesis and secretion of hCG in the human trophoblast at term.

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Secretion and Metabolism of Steroids in Primate Mammals During Pregnancy

Albrecht¹,

Pepe²

1998

Endocrinology of Pregnancy

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Formation of Progesterone and Pregnenolone From [4-14c]cholesterol by the Intact Mid-Term Human Foeto—placental Unit Perfused in Vitro

Cited by 4 publications

References 19 publications

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

Effects of Prolactin on Secretion and Synthesis of Human Chorionic Gonadotropin in Human Term Placentas in vitro: Short-Term Increase in Secretion, Followed by Medium-Term Suppression of Synthesis and Secretion

Secretion and Metabolism of Steroids in Primate Mammals During Pregnancy

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