Info

ß-Lipotropin

Fat

Physiologic role not established

function of testes as well as ovaries. In women FSH promotes growth of ovarian follicles and in men it promotes formation of spermatozoa by the germinal epithelium of the testis. In women LH induces ovulation of the ripe follicle and formation of the corpus luteum from remaining glomerulosa cells in the collapsed, ruptured follicle. It also stimulates synthesis and secretion of the ovarian hormones estrogen and progesterone. In men LH stimulates secretion of the male hormone, testosterone, by interstitial cells of the testis. The actions of these hormones are discussed in detail in Chapters 45 and 46.

The three glycoprotein hormones are synthesized and stored in pituitary basophils and, as their name implies, each contains sugar moieties covalently linked to asparagine residues in the polypeptide chains. All three are comprised of two peptide subunits, designated a and p, which, though tightly coupled, are not covalently linked. The a-subunit is common to all three hormones, and is the product of a single gene located on chromosome 6. The p-subunits of each are somewhat larger than the a-subunit and confer physiologic specificity. Both a- and p-subunits contribute to receptor binding and both must be present in the receptor binding pocket to produce a biological response.

P-Subunits are encoded in separate genes located on different chromosomes: TSH p on chromosome 1, FSH P on chromosome 11, and LH p on chromosome 19, but there is a great deal of homology in their amino acid sequences. Both subunits contain carbohydrate moieties that are considerably less constant in their composition than are their peptide chains. a Subunits are synthesized in excess over p-subunits, and hence it is synthesis of p-subunits that appears to be rate limiting for production of each of the glycoprotein hormones. Pairing of the two subunits begins in the rough endoplasmic reticulum and continues in the Golgi apparatus, where processing of carbohydrate components of the subunits is completed. The loosely paired complex then undergoes spontaneous refolding in secretory granules into a stable, active hormone. Control of expression of the a- and p-subunit genes is not perfectly coordinated, and the free a- and the p-subunits of all three hormones may be found in blood plasma.

The placental hormone, human chorionic gonado-tropin (hCG), is closely related chemically and functionally to the pituitary gonadotropic hormones. It, too, is a glycoprotein and consists of an a and a p chain. The a chain is a product of the same gene as the a chain of pituitary glycoprotein hormones. The peptide sequence of the ft chain is identical to that of LH except that it is longer by 32 amino acids at its carboxyl terminus. Curiously, although there is only a single gene for each ft-subunit of the pituitary glycoprotein hormones, the human genome contains 7 copies of the hCG ft gene, all located on chromosome 19 in proximity to the LH ft gene. Not surprisingly, hCG has biological actions that are similar to those of LH (Chapter 47).

Growth Hormone and Prolactin

Growth hormone (GH) is required for attainment of normal adult stature (see Chapter 44) and produces metabolic effects that may not be directly related to its growth-promoting actions. Metabolic effects include mobilization of free fatty acids from adipose tissue and inhibition of glucose metabolism in muscle and adipose tissue. The role of GH in energy balance is discussed in Chapter 42. Somatotropes are by far the most abundant anterior pituitary cells, and they account for about half of the cells of the adenohypophysis. GH, which is secreted throughout life, is the most abundant of the pituitary hormones. The human pituitary gland stores between 5 and 10 mg of GH, an amount that is 20-100 times greater than other anterior pituitary hormones. Structurally, GH is closely related to another pituitary hormone, prolactin (PRL), which is required for milk production in postpartum women (see Chapter 47). The functions of PRL in men or nonlactating women are not firmly established, but a growing body of evidence suggests that it may stimulate cells of the immune system. These pituitary hormones are closely related to the placental hormone human chorionic somatomammotropin (hCS), which has both growth-promoting and milk-producing activity in some experimental systems. Because of this property, hCS is also called human placental lactogen (hPL). Although the physiologic function of this placental hormone has not been established with certainty, it may regulate maternal metabolism during pregnancy and prepare the mammary glands for lactation (see Chapter 47).

Growth hormone, PRL, and hCS appear to have evolved from a single ancestral gene that duplicated several times; the GH and PRL genes before the emergence of the vertebrates, and GH and the hCS genes after the divergence of the primates from other mammalian groups. The human haploid genome contains two GH and three hCS genes all located on the long arm of chromosome 17, and a single PRL gene located on chromosome 6. These genes are similar in the arrangement of their transcribed and nontranscribed portions as well as their nucleotide sequences. GH and hCS have about 80% of their amino acids in common, and a region 146 amino acids long is similar in hGH and PRL. Only one of the GH genes (hGH N) is expressed in the pituitary, but because an alternative mode of splicing of the RNA transcript is possible, two GH isoforms are produced and secreted by the somato-tropes. The larger form is the 22-kDa molecule (22K GH), which is about 10 times more abundant than the smaller, 20-kDa molecule (20K GH), which lacks amino acids 32 to 46. The other GH gene (hGH V) appears to be expressed only in the placenta and is the predominant form of GH in the blood of pregnant women. It encodes a protein that appears to have the same biological actions as the pituitary hormone although it differs from the pituitary hormone in 13 amino acids and also in that it may be glycosylated.

Considering the similarities in their structures, it is not surprising that GH shares some of the lactogenic activity of PRL and hCS. However, human GH also has about two-thirds of its amino acids in common with GH molecules of cattle and rats, but humans are completely insensitive to cattle or rat GH and respond only to the GH produced by humans or monkeys. This requirement of primates for primate GH is an example of species specificity and largely results from the change of a single amino acid in GH and a corresponding change of a single amino acid in the binding site in the GH receptor. Because of species specificity, human GH was in short supply for treatment of GH-deficient children until the advent of recombinant DNA technology, which made possible an almost limitless supply.

Adrenocorticotropin Family

Portions of the cortex of the adrenal glands are controlled physiologically by adrenal corticotropic hormone (ACTH), which is also called corticotropin or adrenocorticotropin. This family of pituitary peptides includes a- and ft-melanocyte-stimulating hormones (MSH), ft- and a-lipotropin (LPH), and ft-endorphin. Of these, ACTH is the only peptide whose physiologic role in humans is established. The MSHs, which disperse melanin pigment in melanocytes in the skin of lower vertebrates, have little importance in this regard in humans and are not secreted in significant amounts. ft-LPH is named for its stimulatory effect on mobilization of lipids from adipose tissue in rabbits, but the physiologic importance of this action is uncertain. The 91-amino-acid chain of ft-LPH contains at its carboxyl end the complete amino acid sequence of ft-endorphin (from endogenous morphine), which reacts with the same receptors as morphine.

Get Rid of Gallstones Naturally

Get Rid of Gallstones Naturally

One of the main home remedies that you need to follow to prevent gallstones is a healthy lifestyle. You need to maintain a healthy body weight to prevent gallstones. The following are the best home remedies that will help you to treat and prevent gallstones.

Get My Free Ebook


Post a comment