Endocrine Regulation of Gonadotropin Glycosylation

Ulloa‐Aguirre, Alfredo; Maldonado, Angélica; Damián-Matsumura, Pablo; Timossi, Carlos

doi:10.1016/s0188-4409(01)00319-8

Cited by 71 publications

(40 citation statements)

References 115 publications

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“…GnRH and sex steroids are the main recognized endocrine factors involved in the regulation of FSH polymorphism, particularly, in terms of sialic acid content. Several studies have shown that GnRH induces the release of less sialylated FSH isoforms [19, 20, 21, 22]. Similar effects have been observed after estrogen administration [23, 24].…”

Section: Introductionmentioning

confidence: 63%

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Effect of Dihydrotestosterone on Pituitary Follicle-Stimulating Hormone Isoforms in Adult Male Rats Treated with a Gonadotropin-Releasing Hormone Antagonist

et al. 2003

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The effect of androgens on the oligosaccharide structure of follicle-stimulating hormone (FSH) isoforms was studied in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. Animals were castrated (Cx), and 24 h later were treated with physiological doses of either testosterone propionate (T) or dihydrotestosterone propionate (DHT) (0.25 mg/rat in corn oil, daily, s.c.) for 7 days. The antiandrogen flutamide (F; 5 mg/day/rat, twice a day, s.c.) was administered to either Cx-T or Cx-DHT rats to block androgen action. The GnRH antagonist Org 30276 (Ant; 1 mg/kg/day, s.c.) was injected to both Cx- and Cx-DHT treated rats. FSH serum levels reached normal values in Cx rats treated with either T or DHT, whereas those treated with F retained Cx conditions. Both Cx-Ant and Cx-Ant-DHT treated animals presented normal serum FSH levels. Concanavalin A affinity chromatography was used to isolate pituitary FSH isoforms according to their carbohydrate inner structure. An increased proportion of FSH isoforms bearing complex-type oligosaccharides was observed in Cx rats treated with T or DHT, whereas the proportion of these isoforms was reduced in Cx and Cx-T-F or Cx-DHT-F rats. These results demonstrate that functional androgens are needed to complete the oligosaccharide processing of FSH. In addition, the proportion of the different pituitary FSH isoforms after DHT replacement was equivalent to that found when GnRH action was blocked, indicating that androgens are involved in the regulation of carbohydrate incorporation to the FSH molecule by acting mainly at the pituitary level, independently of GnRH action.

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Section: Introductionmentioning

confidence: 63%

“…FSH microheterogeneity is regulated by the endocrine milieu [19]. GnRH and sex steroids are the main recognized endocrine factors involved in the regulation of FSH polymorphism, particularly, in terms of sialic acid content.…”

Section: Introductionmentioning

confidence: 99%

Effect of Dihydrotestosterone on Pituitary Follicle-Stimulating Hormone Isoforms in Adult Male Rats Treated with a Gonadotropin-Releasing Hormone Antagonist

et al. 2003

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“…Administration of 215 frequent exogenous pulses of GnRH results in increased pituitary (33) and circulating (13) concentrations of less acidic isoforms. Moreover, high circulating estradiol concentrations result in increased pituitary synthesis of less acidic isoforms via reduced expression and activity of enzymes involved in posttranslational processing of FSH (34). Thus, increased hypothalamic GnRH pulse frequency stimulates pituitary release of LH and less acidic FSH isoforms, 220 increasing follicular estradiol synthesis, which in turn has feedback effects on the pituitary to sustain the synthesis and release of less acidic isoforms.…”

Section: A Concentrations 195mentioning

confidence: 99%

Follicle-stimulating hormone isoforms and plasma concentrations of estradiol and inhibin A in dairy cows with ovulatory and non-ovulatory follicles during the first postpartum follicle wave

Butler

Pelton

Knight

et al. 2008

Domestic Animal Endocrinology

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Following parturition, all cows display a wave of ovarian follicular growth, but a large proportion fail to generate a preovulatory rise in estradiol, and hence fail to ovulate. Follicle stimulating hormone (FSH) exists as multiple isoforms in the circulation depending on the type and extent of glycosylation, and this has pronounced effects on its biological properties. This 5 study examined differences in plasma FSH, estradiol, and inhibin A concentrations, and the distribution of FSH isoforms in cows with ovulatory or atretic dominant follicles during the first postpartum follicle wave. Plasma FSH isoform distribution was examined in both groups during the period of final development of the dominant follicle by liquid phase isoelectric focusing.Cows with an ovulatory follicle had higher circulating estradiol and inhibin A concentrations, 10 and lower plasma FSH concentrations. The distribution of FSH isoforms displayed a marked shift toward the less acidic isoforms in cows with ovulatory follicles. A higher proportion of the FSH isoforms had a pI >5.0 in cows with ovulatory follicles compared to those with atretic follicles. In addition, cows with ovulatory follicles had greater dry matter intake, superior energy balance, elevated circulating concentrations of insulin and insulin-like growth factor-I, 15 and lower plasma nonesterified fatty acids. The shift in FSH isoforms toward a greater abundance of the less acidic isoforms appears to be a key component in determining the capability for producing a preovulatory rise in estradiol, and this shift in FSH isoforms was associated with more favorable bioenergetic and metabolic status.

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“…Undeniably, among all the glycoprotein hormones, eCG is the most heavily glycosylated with 45% carbohydrate by weight versus 30% for eLH (Bousfield et al 1996;Hokke et al 1994). The nature of oligosaccharide side chains plays an imperative role in the processing and biological activity of the respective hormones (Ulloa-Aguirre et al 2001). The chorionic gonadotropin, expressed in the placenta of higher primates (Maston and Ruvolo 2002), is indispensable for positive advancement of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization, modeling, in silico analysis of equine pituitary gonadotropin alpha subunit and docking interaction studies with ganirelix

Bhardwaj

Nayan

Sharma

et al. 2017

In Silico Pharmacol.

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Equine pituitary gonadotropins (eLH, eFSH, eCG) are heterodimeric glycoprotein hormones with alpha (a) and beta (b) subunits. It is responsible for maintenance of pregnancy in mares during early gestation and fairly valuable for inducing superovulation in animals other than equines. The alpha subunit is common, while beta subunit is species-specific in all glycoprotein hormones. In the present investigation, molecular cloning and in silico characterization including homology modeling and molecular docking analysis of the equine chorionic gonadotropin (eCG) alpha subunit was carried out for gaining structural and functional insights into the eCG alpha subunit and its possible interaction with ganirelix, a gonadotropin-releasing hormone (GnRH) antagonist. The equine chorionic gonadotropin (eCG) alpha subunit expressed in pituitary gland was selected, amplified from total RNA, cloned and sequenced. The in silico analyses were made for homology modelling, structural details, epitope identification and chromosomal localization. Molecular docking studies of eCG alpha were undertaken with a drug ganirelix which is used to control ovulation and has antagonistic activity against GnRH. The protein sequence corresponding to selected open reading frame (ORF) was 99-100% similar with domesticated horse, Przewalski's horse, and 92-93% with Burchell's zebra and donkey. Molecular docking studies revealed the possible interaction of eCG alpha with ganirelix. The possible drug-macromolecule interactions were visualized between eCG alpha and ganirelix. The study will provide structural insight into unique sites and an alternate route of gonadotropin suppression applicable to assisted reproductive technologies.Keywords Equine Á Gonadotropin Á In silico Á Ganirelix Á Docking Anuradha Bhardwaj and Varij Nayan contributed equally to this work.Electronic supplementary material The online version of this article

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Endocrine Regulation of Gonadotropin Glycosylation

Cited by 71 publications

References 115 publications

Effect of Dihydrotestosterone on Pituitary Follicle-Stimulating Hormone Isoforms in Adult Male Rats Treated with a Gonadotropin-Releasing Hormone Antagonist

Effect of Dihydrotestosterone on Pituitary Follicle-Stimulating Hormone Isoforms in Adult Male Rats Treated with a Gonadotropin-Releasing Hormone Antagonist

Follicle-stimulating hormone isoforms and plasma concentrations of estradiol and inhibin A in dairy cows with ovulatory and non-ovulatory follicles during the first postpartum follicle wave

Molecular characterization, modeling, in silico analysis of equine pituitary gonadotropin alpha subunit and docking interaction studies with ganirelix

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