Follicle stimulating hormone

Description

Gonal-F was launched in Austria, Germany, Denmark, Ireland, Italy, Norway, Sweden, Switzerland, France and the UK for the treatment of infertility. The recombinant follicule stimulating hormone (recFSH) was produced by introducing the genes for the α- and β-FSH subunits into the genome of Chinese hamster ovary cells. The isolated recFSH was a glycosylated bioactive dimer that appeared to be identical to urinary human FSH. Biochemically, the recFSH was equal to or slightly better to the uroFSH. The ultra-high purity of recFSH makes it less prone to side effects from contaminants in uroFSH and can be injectable.

Description

Puregon was launched in Denmark, Germany and the UK for ovulation induction in clomiphene-resistent anovulation and controlled ovarian hyperstimulation. Transfected Chinese hamster ovary cells with plasmids containing the genes encoding the α- and β-FSH subunits produced recFSH that was similar to uroFSH. In both cases (follitropin α and β) no antibody formation was detected, however, this form appeared to be more active than follitropin α in that there was a 25% greater pregnancy rate compared to uroFSH.

Chemical properties

Solid; soluble in water.

Originator

Genzyme (Switzerland)

Originator

Organon (Netherlands)

The Uses of Follicle stimulating hormone

Follicle stimulating hormone (FSH) from human pituitary has been used for-

• in vitro luteinization of Macaque granulosa cells
• luteal cell proliferation assay
• culturing of preantral follicle cells obtained from mice
• in vitro maturation of immature cumulus-oocyte complexes (COCs) obtained from mice and
• culture of RAW264.7 cell line

The Uses of Follicle stimulating hormone

A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consi

The Uses of Follicle stimulating hormone

Recombinant human FSH is used for the treatment of infertility and to stimulate follicular development. Recently, it has been well known that the majority of gonadotroph adenomas are clinically silent/nonfunctioning and difficult to identify. They are poorly differentiated and produce and secrete hormones inefficiently. These hormones include FSH β-, LH β-, and GPH α-subunits.

Definition

A gonadotropic glycoprotein secreted by the anterior pituitary gland. It regulates the metabolic activity of the granulosa of the mammalian ovary; stimulates maturation of ovarian follicles, and production of estrogens. Spermatogenesis is partially under

brand name

Humegon (Organon); Pergonal (Serono).

Biological Functions

Follitropins are hormonal products that consist entirely of FSH and are used to stimulate ovarian follicle growth in women who do not have primary ovarian failure. In the absence of an adequate endogenous LH surge, however, hCG must be given following the use of follitropins to stimulate ovulation.

General Description

The α chain of FSH?has 89 amino acids and the β chain has 115 amino acids. The α chain is not active. FSH belongs to glycoprotein hormone family. It is secreted by the gonadotropic cells of pituitary gland.

Biochem/physiol Actions

FSH (follicle stimulating hormone) in involved in the growth of ovarian follicles and steroidogenesis of ovaries. FSHR (follicle stimulating hormone receptor) interacts with FSH in the ovaries, and determines the responsiveness to this hormone. Depressed levels of FSHR result in poor responsiveness and influence folliculogenesis. In Caucasian population, certain polymorphisms in FSHR gene are more commonly found in patients with polycystic ovary syndrome (PCOS). In male fetus and neonates, it facilitates the proliferation of Sertoli cells. In pubescent males, it stimulates spermatogonia to undergo mitosis.

Clinical Use

The gonadotropin follicle-stimulating hormones (FSH), follitropin alfa (Gonal-F) and follitropin beta (Follistim), are produced in the anterior lobe of the pituitary gland. FSH can function in two ways. On the one hand, it causes increased spermatogenesis in men. On the other hand, in concert with estrogen and luteinizing hormone (LH), it stimulates follicular growth and development in women. Consequently, FSH may be useful in the treatment of infertility. FSH is a member of a superfamily of proteins, all structurally related, which includes LH, chorionic gonadotropin, and thyroid-stimulating hormone (TSH).

Purification Methods

FSH is purified by Sephadex G100 gel filtration followed by carboxymethyl-cellulose with NH4OAc pH 5.5. The latter separates luteinising hormone from FSH. Its solubility in H2O is 0.5%. It has an isoelectric point of 4.5. A solution of 1mg in saline (100mL) can be kept at 60o for 0.5hour. Activity is retained in a solution at pH 7-8 for 0.5hour at 75o. The activity of a 50% aqueous EtOH solution is destroyed at 60o in 15minutes. [Bloomfield et al. Biochim Biophys Acta 533 371 1978, Hartree Biochem J 100 754 1966, Pierce & Parsons Ann Rev Biochem 50 465 1981.]