Figure 1 shows the human gene cluster that encodes pituitary growth hormone and three related proteins produced in the placenta (the fifth gene, Pl-L, is a pseudogene with a nonfunctional splice junction). Placental growth hormone, PGH (GH-V, with the V standing for variant), differs from the pituitary protein in only 13 amino acids. The genes for PL-A and PL-B encode the same mature protein product, a glycoprotein containing 191 amino acids, which is 85% identical to pituitary growth hormone.

Fig1. The human growth hormone/placental lactogen gene cluster. The figure depicts the five genes in the 66-kb cluster, located on the long arm of chromosome 17 and the proteins they encode: pituitary growth hormone (GH-N); placental growth hormone (GH-V); placental lactogen (PL-A and PL-B which are identical proteins); and PL-L, a nonfunctional protein encoded by a pseudogene. All five genes are oriented in the same transcriptional direction and each consists of five exons and four introns, having arisen from a common ancestral gene. Placental lactogen is also known as chorionic somatomammotrophin, CS, and the human gene bears this name. The locus control region, LCR, lies 14–32 kb upstream of the first gene in the cluster. The relative amount of total cellular mRNA expressed from each gene in either the pituitary or the placenta is shown in the bottom line.

The growth hormone gene cluster is controlled by a remote upstream locus control region which contains five hypersensitive sites: two of these are specific for pituitary expression of GH-N, another is specific for the placental cluster, and two are active in both tissues. These are the sites at which chromosomal alterations (e.g., histone acetylation and removal, making the sites available to transcription factors) leading to changes in gene expression are initiated. As expected, the patterns of these and con sequent alterations differ for the five genes in the cluster.

Placental lactogen (hPL) is first detectable in the placenta at about 18 days after fertilization and in the maternal circulation at 5–6 weeks. As shown in Figure 2 the levels of hPL rise throughout pregnancy. In fact it has been shown that the amount of maternal circulating hPL is exactly proportional to placental mass and, as shown in Figure 1, at least 3% of placental mRNA encodes this hormone. As term approaches, the secretion rate of hPL approaches 1.0 gram/day, greater than that of any other protein hormone; hPL becomes nondetectable in maternal blood within one day of the delivery of the placenta. A small amount of hPL is secreted into the fetal circulation, where levels also rise during the pregnancy, but are about 1000-fold lower than those in the maternal circulation.

Fig2. Chorionic gonadotrophin and placental lactogen levels during pregnancy. The graph shows the levels of human chorionic gonadotrophin (hCG) and placental lactogen (hPL) throughout pregnancy. hPL is also known as chorionic somatomammotrophin, CS or hCS. hCG is detectable a few days following fertilization, rises exponentially to a peak at about 8 weeks, then declines to a plateau for the remainder of the pregnancy. hPL is first detectable at about 5 weeks and continues to rise until term.

Maternal serum levels of placental growth hormone (PGH; GH-V) are three orders of magnitude lower than those of hPL and it cannot be detected in maternal serum until about 22 weeks. PGH increases exponentially during the last trimester of pregnancy; at the same time maternal pituitary growth hormone falls to undetectable levels. It is likely that this suppression of maternal GH secretion is the result of the negative feedback effect of increased IGF-1 (about two-fold from week 25 to term) in response to both hPL and PGH. Maternal pituitary GH levels (GH-N) return to normal within 48 hours of delivery. No PGH is found in the fetus.

Although hPL was originally identified by its lactogenic properties in rodents and in bioassays using cells in tissue culture, a role for the hormone in lactogenesis in humans has not been clearly established. It is, however, known to alter maternal metabolism leading to the diabetogenic state of pregnancy in which fuels, especially glucose, are preferentially made available for the fetus. Features of this state include decreased glucose tolerance, decreased insulin sensitivity, and increased lipolysis in adipocytes with increased availability of free fatty acids. The latter are used by the mother to spare glucose for the fetus and also are made available to the fetus, along with the ketone bodies that result from their oxidation by the mother, providing additional fuels for the fetus.

These effects of hPL are similar to those of growth hormone, including PGH. Since no receptor for specific PL receptors has been identified, it is thought that hPL, PGH, and GH share the same receptor. Although hPL binds to the GH receptor with relatively low affinity, the large amounts of the hormone could be sufficient to activate the receptor. Women with inactivating mutations of hPL deliver normal babies while those missing both PGH and hPL have babies of very low birth weight. There have been no reported cases of women lacking only PGH. Taken together, these observations suggest that even though hPL is normally produced in very high amounts, its absence is compensated for by the presence of PGH, indicating some redundancy in the important function of providing fuel for the fetus from the maternal metabolic system.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية يصدر عددين جديدين من نشرتي الكفيل والخميس

متحف الكفيل يستعرض حاملَ شموعٍ يعود إلى العصر القاجاري

ذوو شهداء مدرسة ميناب الإيرانية يتشرفون بزيارة مرقد أبي الفضل العباس (عليه السلام)

قسم الصناعات ينجز 75‎%‎ من أعمال إنشاء سور حديدي في شركة عين الحياة

المزيد

الآخبار الصحية

السجائر الإلكترونية والإقلاع عن التدخين.. نتائج متباينة تثير الجدل العلمي

مصر تحقق إنجازاً دولياً جديداً في منظمة الصحة العالمية

دراسة: السباحة فعّالة أكثر من الجري في الحفاظ على صحة القلب

عامل خطر في بداية الحمل يؤخر تطور الكلام والمهارات الحركية لدى الرضع

المزيد

الآخبار التكنلوجية

أحلامك ليست عشوائية.. إليك ما يفعله دماغك أثناء نومك

روسيا.. العلماء يضاعفون الاستقرار الحراري للألواح الشمسية ثلاث مرات

علماء يكشفون سر سرعة الدلافين في السباحة

سلمي أو دموي.. هكذا تنتقل السلطة في مجتمع الجرذان

المزيد

مواضيع ذات صلة

Maternal Adaptations to Pregnancy

Human Chorionic Gonadotrophin

Polycystic Ovary Syndrome (PCOS)

Estrogen and the Cardiovascular System

Effects of Estrogen on Bone

Uterine Effects of Estrogen and Progesterone

Menopause

Chemistry and Metabolism of Female Steroid Hormones: Feedback Effects on the Hypothalamus and Pituitary

Control of the Ovary by the Hypothalamus and Pituitary

Synthesis of Progesterone and Estrogens

Female Steroid Hormones

The Androgen Receptor