Archives of Medical Research 32 (2001) 520–532 0188-4409/01 $–see front matter. Copyright © 2001 IMSS. Published by Elsevier Science Inc. PII S0188-4409(01)00319-8 REVIEW ARTICLE Endocrine Regulation of Gonadotropin Glycosylation Alfredo Ulloa-Aguirre, a Angélica Maldonado, a Pablo Damián-Matsumura a,b and Carlos Timossi a a Research Unit in Reproductive Medicine, Hospital de Gineco-Obstetricia Luis Castelazo Ayala, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico b Department of Reproductive Biology, Universidad Autónoma Metropolitana-Iztapalapa (UAM-Iztapalapa), Mexico City, Mexico Received for publication May 31, 2001; accepted June 1, 2001 (01/079). The pituitary gonadotropins—luteinizing hormone and follicle-stimulating hormone—as well as the placental choriogonadotropin belong to the family of glycoprotein hormones. These structurally related hormones, which regulate several major reproductive functions of the body, are heterodimers consisting of a common -subunit noncovalently bound to a -subunit. The N- and O-linked oligosaccharide chains of these gonadotropins play an im- portant role in intracellular folding, assembly, secretion, metabolic clearance, and biologi- cal activity of the hormone. Gonadotropin glycosylation is a highly complex process; within the gonadotropes it is modulated by a variety of extrapituitary factors of hypotha- lamic and gonadal origin. In particular, estrogens and androgens appear to regulate termi- nal sialylation and/or sulfation of the oligosaccharide attachments and hence some func- tional properties of the gonadotropin molecule determined by these residues, i.e., metabolic clearance and in vivo biopotency. Through these extrapituitary inputs, the ante- rior pituitary may not only regulate the quantity but also the quality of the gonadotropin signal delivered to the gonads in a given physiologic or pathologic condition. © 2001 IMSS. Published by Elsevier Science Inc. Key Words: Glycosylation, Gonadotropins, Carbohydrates, Anterior pituitary. Introduction The gonadotropins, luteinizing hormone (LH), follicle-stim- ulating hormone (FSH), and choriogonadotropin (CG) are the hormones or endocrine signals that regulate gonadal function. Luteinizing hormone and FSH are produced by a heterogeneous group of cells, the gonadotropes of the ante- rior pituitary (1,2). Although CG is synthesized mainly by the placental trophoblasts, there is compelling evidence in- dicating that this gonadotropin is also normally produced by the anterior pituitary (3–5); CG is found only in primates and equids, while the pituitary gonadotropins are found in all mammals and in some non-mammalian species (6,7). Both LH and FSH play an essential role in regulating go- nadal function; their coordinated secretion and action allow for an extremely precise control of ovarian and testicular function. Granulosa and Sertoli cells are the targets for FSH; in these cells, FSH promotes the synthesis of estro- gens and several non-steroidal factors as well as gametoge- nesis. The main target tissues for LH are the testicular Ley- dig cells and several ovarian cell types, in which this gonadotropin regulates the local and systemic concentra- tions of sex steroids, mainly androgens and progesterone, as well as some nonsteroidal factors. Luteinizing hormone is also essential for follicular rupture and the subsequent re- lease of the oocyte. The placental gonadotropin, CG, is se- creted by the trophoblasts early in pregnancy and maintains steroid production by the corpus luteum until the placenta is functionally competent and assumes the aforementioned function later in pregnancy. Luteinizing hormone, FSH, and CG as well as thyroid- stimulating hormone (TSH)—produced by a distinct ante- rior pituitary cell type, the thyrotrope—comprise a well- defined, structurally related family of glycoproteins (2,8). All are heterodimers consisting of a common -subunit noncovalently bound to a -subunit (2,8). Within a given Address reprint requests to: Alfredo Ulloa-Aguirre, M.D., D.Sc., Research Unit in Reproductive Medicine, IMSS, Apdo. Postal 99-065, Unidad Independencia, 10101 México, D.F., México. Phone and FAX: (+52) (55) 5616-2278; E-mail: aulloaa@conacyt.mx