FSH is synthesized and secreted by the anterior pituitary gland in multiple molecular forms; the release of these isoforms depends on the endocrine status of the donor at the time of sample collection. In the present study, we analysed the possibility that the FSH charge isoforms may exert differential effects at the target cell. Seven FSH isoform mixes were isolated from pooled anterior pituitary glycoprotein extracts by high resolution chromatofocusing, followed by affinity chromatography, which removed nearly 90% of the LH that co-eluted with the FSH isoforms during chromatofocusing. The isoforms (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 4·76-4·12; VI, pH 4·05-3·82 and VII, pH <3·80) were then tested for their capacity to stimulate cAMP release, androgen aromatization and tissue-type plasminogen activator (tPA) enzyme activity and cytochrome P450 aromatase, tPA and inhibin -subunit mRNA production by rat granulosa cells in culture. cAMP and oestradiol production were determined by RIA, tPA enzyme activity by SDS-PAGE and zymography and all mRNAs by northern blot hybridization analysis and semiquantitative RT-PCR. All isoforms, with the exception of isoform I, stimulated synthesis and release of cAMP, oestrogen and tPA enzyme activity in a dosedependent manner; the potency of the less acidic isoforms (pH 6·60-4·60) was greater than that exhibited by the more acidic/sialylated analogs (pH 4·76 to <3·80; potencies II>III>IV>V>VII>VI). A similar trend was observed in terms of cytochrome P450 aromatase and tPA mRNA production. In contrast, when FSH-stimulated production of -inhibin mRNA was analysed, isoforms V-VII were significantly more potent (two-to threefold) than the less acidic/sialylated counterparts (II-IV). In contrast to isoforms II-VII (which behaved as FSH agonists), isoform I (elution pH >7·10) completely blocked P450 aromatase and tPA mRNA expression, without altering that of a constitutively expressed gene (glyceraldehyde-3-phosphate dehydrogenase). These results show for the first time that the naturally occurring human FSH isoforms may exhibit differential or even unique effects at the target cell level.

Summary: Liver damage and alterations in the exocrine function of the gland lead to a profound alteration of the plasma lipoprotein profile. To determine whether hepatic disease results in changes in the lipoprotein fatty acid composition, i. e. to determine whether liver function influences the homeostasis of complex lipids in plasma, we studied the fatty acid profile of lipids from VLDL, LDL and HDL, as well as from total plasma, in thirty-one patients of both sexes with hepatobiliary pathology (compensated liver cirrhosis, uncompensated liver cirrhosis, primary biliary cirrhosis, other intrahepatic cholestasis, and acute viral hepatitis). We also studied a group of healthy adults as controls. We present the lipoprotein profile and the fatty acid composition (myristic C14, palmitic C16, palmitoleic C16 : 1, stearic CIS, oleic CIS : 1, linoleic CIS : 2, eicosatrienoic C20 : 3co6 and arachidonic C20 : 4) of lipoprotein and total plasma triacylglycerols, cholesteryl esters and phospholipids. The main observation of this study is that, despite the profound changes in the lipoprotein profile and the lower abundance of polyunsaturated fatty acids in complex lipids, the composition of all triagylglycerols, cholesteryl esters and phospholipids is very similar for the corresponding lipoproteins of patients with hepatobiliary disease and of control subjects. This indicates that in the controls as in the studied patients, the exchange of lipids between plasmatic lipoproteins is very rapid and demonstrates the possible importance of the extrahepatic synthesis of cholesteryl ester transfer protein.