The release of the sulfated form of the inactive androgen dehydroepiandrosterone sulfate (DHEAS) primarily occurs in the fetal zone during most of gestation. This release is dependent on fetal ACTH from the fetal pituitary by the end of the first trimester. The fate of DHEAS involves two pathways. Firstly, it can go directly to the syncytiotrophoblast where it is desulfated by placental steroid sulfatase. It is then used as a 19-carbon substrate for the synthesis of estradiol-17β and estrone. Secondly, DHEAS undergoes 16-hydroxylation in the fetal liver by the enzyme CYP3A7. The 16-hydroxyl-DHEAS is then converted by syncytiotrophoblasts to estriol, the major estrogen of pregnancy. In X-linked ichthyosis, a condition where the steroid sulfatase is low or missing, the active estrogen production by the fetoplacental unit is lost. This results in a prolonged pregnancy that usually ends with physician-induced labor. The baby boy with this condition has a treatable skin disorder called ichthyosis. Throughout pregnancy, maternal estrogen levels increase. Estriol levels can be used as an indicator of fetal health as estrogen production relies on a healthy fetus. The term "fetoplacental unit" refers to the placental syncytiotrophoblasts and fetal organs involved in estrogen production. Estrogens have several effects on maternal physiology, including increasing uteroplacental blood flow, enhancing LDL receptor expression in syncytiotrophoblasts, and inducing components involved in parturition. Estrogens also stimulate breast growth and prolactin production in the maternal pituitary. Additionally, estrogens affect various other aspects of maternal physiology. Human placental lactogen (hPL), also known as human chorionic somatomammotropin (hCS), is a protein hormone produced in the syncytiotrophoblast that is structurally similar to growth hormone (GH) and prolactin (PRL). Its function overlaps with GH and PRL and its levels can be detected within the syncytiotrophoblast and maternal serum during early pregnancy. Maternal serum levels of hPL progressively rise throughout pregnancy and its secretion is directly related to the size of the placenta. hPL is protein anabolic and lipolytic, and its antagonistic action to insulin is responsible for the diabetogenicity of pregnancy. Like PRL, hPL stimulates mammary gland growth and development. hPL also inhibits maternal glucose uptake and use, resulting in increased serum glucose levels. This is important as glucose is a major energy substrate for the fetus, and hPL increases fetal glucose availability.
Fig. 44.35 ). The fetal zone primarily releases the sulfated form of the inactive androgen dehydroepiandrosterone sulfate (DHEAS) throughout most of gestation. Production of DHEAS from the fetal adrenal is absolutely dependent on fetal ACTH from the fetal pituitary by the end of the first trimester.
The DHEAS released from the fetal zone has two fates. First, DHEAS can go directly to the syncytiotrophoblast, where it is desulfated by a placental steroid sulfatase and used as a 19-carbon substrate for the synthesis of estradiol-17β and estrone (see
Fig. 44.35 ). The second fate of DHEAS is 16-hydroxylation in the fetal liver by the enzyme CYP3A7. 16-Hydroxyl-DHEAS is then converted by syncytiotrophoblasts to the major estrogen of pregnancy, estriol (see
Fig. 44.35 ). In X-linked ichthyosis, the steroid sulfatase is low or missing, resulting in loss of active (i.e., desulfated) estrogen production by the fetoplacental unit. Pregnancy is normal, but because estrogens promote parturition, the pregnancy is prolonged and usually ends with physician-induced labor. The baby boy has a skin disorder of varying degrees of severity that is called ichthyosis (scaly skin), owing to buildup of layers of shed cells within the stratum corneum. This form of ichthyosis is readily treatable by topical creams.
Maternal estrogen levels increase throughout pregnancy. Because estrogen production is dependent on a healthy fetus, estriol levels can be used as one measure of fetal health. The collective term used for the placental syncytiotrophoblasts and fetal organs in the context of estrogen production is the fetoplacental unit. Estrogens increase uteroplacental blood flow, enhance LDL receptor expression in syncytiotrophoblasts, and induce several components (e.g., prostaglandins, oxytocin receptors) involved in parturition. Estrogens increase breast growth directly and indirectly through stimulation of maternal pituitary prolactin production. Estrogens also increase lactotrope size and number, thereby increasing overall pituitary mass by more than twofold by term. Estrogens also affect several other aspects of maternal physiology.
Human placental lactogen (hPL), also called human chorionic somatomammotropin (hCS), is a 191–amino acid protein hormone produced in the syncytiotrophoblast that is structurally similar to growth hormone (GH) and prolactin (PRL). Its function overlaps those of both GH and PRL. It can be detected within the syncytiotrophoblast by 10 days after conception and in maternal serum by 3 weeks’ gestation (see
Fig. 44.34 ). Maternal serum levels rise progressively throughout the remainder of the pregnancy. The quantity of hormone produced is directly related to the size of the placenta, such that as the placenta grows during gestation, hPL secretion increases. As much as 1 g/day of hPL can be secreted late in gestation.
Like GH, hPL is protein anabolic and lipolytic. Its antagonistic action to insulin is the major basis for the diabetogenicity of pregnancy. Like PRL, it stimulates mammary gland growth and development. Mammary gland development in pregnancy results from the actions of hPL, PRL, estrogens, and progestins. hPL inhibits maternal glucose uptake and use, thereby increasing serum glucose levels. Glucose is a major energy substrate for the fetus, and hPL increases fetal glucose availability.
CHAPTER 44 The Male and Female Reproductive Systems