HLH

Structure

LH is a glycoprotein consisting of noncovalently linked glycoprotein hormone (GPH) α- and LH β-subunits. The GPH α-subunit is common to folliclestimulating hormone (FSH), thyroid-stimulating hormone (TSH), and chorionic gonadotropin (CG). The LH β-subunit contains a cysteine-knot motif, which is critical for the heterodimer assembly and biological activity of the hormone. The N-linked oligosaccharide chain is important for the intracellular folding, secretion, metabolic clearance, and biological activity of the hormone. Mr 26,000–48,000. pI: human LH, 7.2–9.2; rat LH, 8.6–9.3; pig LH, 7.2–9.2; horse LH, 4.5–7.5. Multiple isoforms exist due to the microheterogeneity of oligosaccharide chains. Soluble in water; insoluble in alcohol and acetone. Partially (50%) dissociated to two subunits at pH 1.9. Inactivated by oxidation (hydrogen peroxide, periodic acid), reduction (cysteine, ketone), and treatment with trypsin, chymotrypsin, and pepsin. Picrolonic, flavianic, picric, and trichloroacetic acids precipitate LH with retention of its activity.

Gene, mRNA, and precursor

The human LH β-subunit gene, LHB, location 2p21, consists of three exons. The human LH β-subunit mRNA has 523 b that encode a signal peptide of 20 aa residues and a mature protein of 121 aa residues. The LH β-subunit gene is expressed in the basophilic gonadotropes in the anterior pituitary. In tetrapods, FSH and LH are coexpressed in gonadotropes, whereas they are produced in different cells in teleosts.

Receptors

The receptor of LH (LHR) is a glycoprotein that belongs to a subclass of the rhodopsin/β-adrenergic subfamily of the membrane-bound GPCR superfamily. The LHR consists of around 700 aa residues and contains a large N-terminal extracellular domain (~360 aa residues), seven transmembrane domains, and a C-terminal intracellular domain.  The receptor mainly couples to the Gs protein, and LH stimulates the production of cAMP in target cells.

Agonists and Antagonists

hCG, and purified and recombinant human LH, are agonists. Deglycosylated hCG and deglycosylated LH are antagonists.

Clinical implications

A single mutation (Gly 578 Asp) in the sixth transmembrane domain of LHR resulting in the constitutive activation of the LHR causes familial male precocious puberty.16 A missense mutation (Ala 593 Pro) in the sixth transmembrane domain of LHR causes Leydig cell hypoplasia. Conditions with high LH levels include premature menopause, gonadal dysgenesis, Turner syndrome, castration, Swyer syndrome, polycystic ovary syndrome, certain forms of congenital adrenal hyperplasia, testicular failure, and pregnancy. Conditions with low FSH levels include Kallmann syndrome, hypothalamic suppression, hypopituitarism, eating disorders, female athlete triad, hyperprolactinemia, and hypogonadism.

Synthesis and release

The synthesis and release of LH are regulated by GnRH, gonadotropin-inhibitory hormone (GnIH), gonadal steroids, and dopamine. In tetrapods, GnRH acts directly on gonadotropes and differentially regulates LH and FSH secretion through changes in the pattern of GnRH pulsatile secretion. GnIH inhibits LH secretion in birds and mammals, whereas GnIH can stimulate and inhibit LH secretion in fish depending on the species and reproductive status. LH secretion is regulated by gonadal steroids such as estradiol and testosterone. Gonadal steroids exert their effects at the level of the hypothalamus by changing GnRH secretion, and directly at the level of the gonadotropes, where they exert different effects depending on the species and reproductive condition of animals. In teleosts, dopamine inhibits both basal and GnRH-stimulated LH secretion.

Description

This is a gonadotropic glycoprotein hormone secreted from the anterior pituitary. In females, an LH surge triggers ovulation and stimulates the development of the corpus luteum. In males, LH stimulates androgen production and spermatogenesis. Gonadotropic fractions with the properties of LH were purified from the ovine in the late 1950s, and subsequently LH has been isolated from many other species. Human LH was first fully purified in 1964. The aa sequence of the ovine LH β-subunit was determined in 1972. The full nucleotide sequence of the human LH β-subunit gene was determined in 1984.

Uses

A surge of LH is tested to predict ovulation using urinary ovulation predictor kits. Recombinant human LH is used for the treatment of female infertility. Menotropins (human menopausal gonadotropin, hMG), a mixture of FSH and LH, are used to treat infertility in women. hCG derived from the urine of pregnant women is used as an LH substitute.

General Description

LH is another glycoprotein. It acts after the maturing actionof FSH on ovarian follicles, stimulates production of estrogens,and transforms the follicles into corpora lutea. LHalso acts in the male to stimulate the Leydig cells that producetestosterone.