Differential effects of the charge variants of human follicle-stimulating hormone

Citation
Cm. Timossi et al., Differential effects of the charge variants of human follicle-stimulating hormone, J ENDOCR, 165(2), 2000, pp. 193-205
Citations number
64
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF ENDOCRINOLOGY
ISSN journal
00220795 → ACNP
Volume
165
Issue
2
Year of publication
2000
Pages
193 - 205
Database
ISI
SICI code
0022-0795(200005)165:2<193:DEOTCV>2.0.ZU;2-8
Abstract
FSH is synthesized and secreted by the anterior pituitary gland in multiple molecular forms; the release of these isoforms depends on the endocrine st atus of the donor at the time of sample collection. In the present study, w e analysed the possibility that the FSH charge isoforms may exert different ial effects at the target cell. Seven FSH isoform mixes were isolated from pooled anterior pituitary glycoprotein extracts by high resolution chromato focusing, followed by affinity chromatography, which removed nearly 90% of the LH that co-eluted with the FSH isoforms during chromatofocusing. The is oforms (isoform I, pH > 7.10; II, pH range 6.60-6.20; III, pH 5.47-5.10; IV , pH 5.03-4.60; V, pH 4.76-4.17; VI, pH 4.05-3.82 and VII, pH <3.80) were t hen tested for their capacity to stimulate cAMP release, androgen aromatiza tion and tissue-type plasminogen activator (tPA) enzyme activity and cytoch rome P450 aromatase, tPA and inhibin a-sub;nit mRNA production by rat granu losa cells in culture. cAMP and oestradiol production were determined by RI A, tPA enzyme activity by SDS-PAGE and zymography and all mRNAs by northern blot hybridization analysis and semiquantitative RT-PCR. AU isoforms, with the exception of isoform I, stimulated synthesis and release of cAMP, oest rogen and tPA enzyme activity in a dose-dependent manner; the potency of th e less acidic isoforms (PH 6.60-4.60) was greater than that exhibited by th e more acidic/sialylated analogs (pH 4.76 to <3.80; potencies II>III>IV>V>V II>VI). A similar trend was observed in terms of cytochrome P450 aromatase and tPA mRNA production. In contrast, when FSH-stimulated production of cr- inhibin mRNA was analysed, isoforms V-VII were significantly more potent (t wo- to threefold) than the less acidic/sialylated counterparts (II-IV). In contrast to isoforms II-VII (which behaved as FSH agonists), isoform I (elu tion pH >7.10) completely blocked P450 aromatase and tPA mRNA expression, w ithout altering that of a constitutively expressed gene (glyceraldehyde-3-p hosphate dehydrogenase). These results show for the first time that the nat urally occurring human FSH isoforms may exhibit differential or even unique effects at the target cell level.