Structure–Function Relationships of Gonadotropins

Ryan, Robert J.; Keutmann, Henry T.; Charlesworth, M. Cristine; McCormick, Daniel J.; Milius, Robert P.; Calvo, Francisco O.; Vutyavanich, Teraporn

doi:10.1016/b978-0-12-571143-2.50016-2

Cited by 81 publications

(57 citation statements)

References 146 publications

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“…In this regard, it may be noted that the subtle changes in conformation following hormone deglycosylation not discernable by many biophysical studies [3,7,8] or studies with other receptors [3,8] could be detected by immunological techniques. These latter studies showed that certain antisera could discriminate glycosylated (active) and deglycosylated (inactive) forms of the hormone [lo-121.…”

Section: Discussionmentioning

confidence: 99%

Hormone glycosylation required for lutropin receptor recognition in sheep testis

1990

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The high affinity binding sites for ovine pituitary lutropin (oLH) present in DLS-1 sheep testis recognized only the fully glycosylated ovine or bovine hormone (bLH) in receptor binding assays using 1251-labeled oLH. Chemically deglycosylated (DG-) oLH or bLH which were fully active with other lutropin receptors (rat/pig) were completely inert in the DLS-1 receptor assay. In the same membranes, the FSH (follitropin) receptor reacted well with both glycosylated FSH and DG-oFSH. In recombination studies, lutropin formed by glycosylated native G(-and B-subunits of the hormone was fully active but when one of the subunits was in the deglycosylated form, receptor binding activity was greatly reduced. The presence of glycosylated a-subunit in the recombined hormone gave rise to 5 x more activity than DG-a+/?. All these preparations were fully active in the rat/pig receptor assays for LH. These results demonstrate that lutropin hormone glycosylation is essential for optimum receptor recognition in the sheep testis, further emphasizing the importance of correct glycosylation in oLHa hormone function.

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Section: Discussionmentioning

confidence: 99%

Hormone glycosylation required for lutropin receptor recognition in sheep testis

1990

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“…Accordingly, all gonadotropins can be assumed to have identical disulfide linkages and similar tertiary structures. However, several proposals have been reported for the disulfide pairing of mammalian lutropins by chemical assignment [12]. Recently, two independent groups determined the three-dimensional structure of human chronic gonadotropin by X-ray crystallography and all disulfide linkages were elucidated [13, 141. According to the X-ray studies, the two subunits have a similar topography, called a cystine knot, formed by three disulfide bridges, Cysl-Cys6, Cys4-Cys8, and CysS-Cys9 for the P-subunit, and Cys2-Cys7, Cys3-Cys8, and Cys5-Cys9 for the a-subunit (Figs 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

Complete Amino Acid Sequences of Follitropin and Lutropin in the Ostrich, Struthio camelus

Koide

Papkoff

Kawauchi

1996

European Journal of Biochemistry

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We determined the complete amino acid sequences of two pituitary gonadotropins, follitropin and lutropin in the ostrich, thereby providing the first information on the structure of avian follitropin. Ostrich follitropin and lutropin both consist of two subunits: a common a-subunit and a hormone-specific Psubunit. The a-subunit is composed of 96 amino acid residues and has 70-80% sequence identity with the a-subunits of most vertebrates. The ostrich follitropin P-subunit consists of 106 amino-acid residues, and shows 70-74% sequence identity with mammalian follitropins P, 61 % with amphibian follitropin p, 39-46% with teleost gonadotropins IIP and 32-44 % with teleost gonadotropins ID. The ostrich lutropin P-subunit consists of 128 amino-acid residues, and exhibits 76-78 % sequence identity with other avian lutropins P, 44-50% with teleost gonadotropins IIP, 45% with amphibian lutropin P, 41-44% with mammalian lutropins P, and 25 -36 % with teleost gonadotropins IP. Sequence comparison revealed that lutropin P-subunits are more class-specific and have divervified approximately twice as fast follitropin Psubunits, although segments essential for maintaining higher-order structures have been conserved.Keywords: amino-acid sequence; Aves; follitropin; lutropin; ostrich.Two homologous gonadotropins, follitropin (follicle-stimulating hormone) and lutropin (luteinizing hormone), regulate the cellular and endocrine functions of the gonads of tetrapods. These gonadotropins are members of a family that also includes thyrotropin, of pituitary origin, and chorionic gonadotropin, of placental origin, and are heterodimers composed of two dissimilar and non-covalently bound glycoproteins, known as the aand P-subunits. The P-subunit is hormone-specific and confers receptor-binding specificity, whereas the a-subunit is common among the hormones within a given species and is highly conserved in several species. The a-subunit conservation suggests that these hormones share a common ancestor and diverged by duplication of the P-subunit gene. Therefore, it is essential to compare the P-subunit structures of many different species in order to understand the molecular evolution and functional divergence of the hormone family. Howevcr, information concerning the molecular structure of gonadotropins, and of follitropin in particular, in non-mammalian tetrapods is limited.In Aves, cDNAs encoding the lutropin subunits of the chicken [l], Japanese quail [2], and turkey [3] have been cloned and sequenced, but no information concerning avian follitropin structure has been reported. Extant birds consist of two lineages,

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“…In general, the terminal carbohydrate residue of gonadotropin oligosaccharides is either sulphated or sialylated [17]. Some hormones, for example bFSH and hFSH, contain a much greater proportion of sialic acid and galactose than sulphate and GalNAc [10,65,66].…”

Section: Sialylated Oligosaccharides In the Pituitary Glycoprotein Homentioning

confidence: 99%

“…4. The position and structure of the Asn-linked carbohydrates found on gonadotropin subunits are varied [17,24,55] and consist of four types: (i) neutral, (ii) sialylated, (iii) sulphated and (iv) mixed sialylated/sulphated types. Oligosaccharides differ not only in their degree of sialylation or sulphation, but also in their core structures; these differences are the basis for the microheterogeneous molecular populations of individual hormones with varying biological activities [27,29,[56][57][58][59][60].…”

Section: Structural Features Of the Asn-linked Carbohydratesmentioning

confidence: 99%

“…immunologically active hormone may not always be biologically active [16]. Immunogenicity of glycoprotein hormones is, for the most part, dependent on a peptide epitope while the carbohydrate moieties contribute to the overall bioactivity of the hormone [9,17,18]. It should follow then, that isoforms of a particular gonadotropin have different bioactivities, due to the variation in carbohydrates found in them.…”

Section: Introductionmentioning

confidence: 99%

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Structural and Functional Roles of FSH and LH as Glycoproteins Regulating Reproduction in Mammalian Species

Mullen¹,

Cooke²,

Crow³

2013

Gonadotropin

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Structure–Function Relationships of Gonadotropins

Cited by 81 publications

References 146 publications

Hormone glycosylation required for lutropin receptor recognition in sheep testis

Hormone glycosylation required for lutropin receptor recognition in sheep testis

Complete Amino Acid Sequences of Follitropin and Lutropin in the Ostrich, Struthio camelus

Structural and Functional Roles of FSH and LH as Glycoproteins Regulating Reproduction in Mammalian Species

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