Immunological and biological potencies of the different molecular species of gonadotrophins

Abstract

Pituitary gonadotrophins (follicle-stimulating hormone, FSH; luteinizing hormone, LH) exist in different molecular forms within the anterior pituitary gland and serum of several non-mammalian and mammalian species, including man. The number and relative abundance of each gonadotrophin species will depend on the specific technique utilized for their isolation, the tissue source and the physiological status of the donor. Intracellular FSH and LH from glands of rodents (hamsters and rats) and primates exhibit charge heterogeneity and therefore may be separated into several forms or iso-hormones by isoelectric focusing (IEF). These FSH and LH species differ from each other not only in their isoelectric point (pI) but also in their relative abundance, receptor binding activity, biological activity and plasma half-life. Almost all gonadotrophin species isolated from pituitary extracts have also been detected in vitro and in vivo as secreted forms. Less basic rodent LH and FSH forms exhibit low receptor binding and in-vitro biological activities; a similar trend is found in LH and FSH species isolated from glands of monkeys and humans. However, these relatively acidic isohormones have longer circulatory half-lives and higher in-vivo biological activities than less negatively charged forms. The overall pattern of charge heterogeneity of gonadotrophins varies according to the specific endocrine status of the donor. Sex steroid hormones (mainly oestrogens) and gonadotrophin-releasing hormone seem to act in concert at the pituitary level to influence the physicochemical and functional characteristics of gonadotrophins and therefore their biological expression at the target cell. The effects of these factors appear to be mediated through the incorporation of specific carbohydrate residues and/or degree of terminal sugar sulphation at co-post-translational levels. The first result of these complex interactions between the gonad and the hypothalamic-pituitary unit is the production and secretion of various types of gonadotrophin molecules in proportions according with the physiological requirements of the subject at a given time, to perform specific actions upon gonadal maturation and/or function.

Androgen Regulation of Immunological and Biological Activities of Pituitary Follicle-Stimulating Hormone Isoforms inMale Rats

“…The polymorphism of follicle-stimulating hormone (FSH) has previously been described in males and females from different species. These studies were mainly based on differences in the isoelectric point determined by the content of sialic acid, the outer terminal sugar of the carbohydrate chain [4, 5, 6, 7]. …”

Immunological and Biological Activities of Pituitary FSH Isoforms in Prepubertal Male Rats: Effect of Antiandrogens

“…This differential glvcosylation, in turn, exerts a marked influence on circulating half-life, receptor binding affinity, and in vitro and in vivo biological activities [5], It has been shown that carbo hydrates are needed for the full expression of the biologi cal activity [6]. Sialic acid determines the circulating halflife of the hormone [7], as well as the receptor affinity in vitro [5], The results obtained in experimental animals as well as in studies carried out in children, adults, and aging men and women under different physiological conditions have shown that the hormonal status regulates the sialic acid content of FSH isoforms [8,9], In males, differences have been demonstrated in charge distribution by castra tion [10,11], antiandrogen administration [12], during sexual maturation [13,14], and by in vitro testosterone treatment [15]. There is no evidence of the hormonal influence upon the carbohydrate inner structure of pitu itary FSH isohormones and the relationship between this carbohydrate inner structure of FSH isohormones and their bioactivity.…”

Single-Dose Pharmacokinetics and Pharmacodynamics of Recombinant Human Follicle-Stimulating Hormone (Org 32489) in Gonadotropin-Deficient Volunteers

“…The 92-amino acid ␣-chain and the 111-amino acid ␤-chain have each two Nlinked oligosaccharide chains presented as complex heterogeneous multiantennary structures (3). The variable degree of glycosylation, especially of sialylation, creates a spectrum of FSH isoforms with differences in charge, bioactivities, and elimination halflives (4,5).…”