FSH分泌の調節機序

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FSH secretion from the pituitary is now generally believed to be controlled only by LH-RH. However, since 1971 I have been publishing lines of evidence suggesting that FSH is controlled by both LH-RH and FSH-RH distinct from LH-RH. Recent accumulated reports suggest that lots of data cannot be explained by the one-RH theory. The one-RH theory means that both LH and FSH are regulated by a sole releasing factor, LH-RH. In 1985 we succeeded in purification of porcine and bovine follicular inhibin for the first time in the world. Its molecular weight was 32,000, which consisted of α-subunit (mw 20,000) and β-subunit (mw 13,000). The site of production of inhibin was confirmed to be granulosa cell by immuno-histochemical technique and to be corpus luteum by RIA. Secretion of inhibin was stimulated by FSH, insulin, platelet extract, dibutyryl c-AMP, cholera toxin, forskolin, and inhibited by cortisol. Testosterone augmented FSH action. In the pituitary cells, inhibin inhibited synthesis of FSH, so cycloheximide could mimicked inhibin action in vitro. Inhibin did not inhibit LH release from the pituitary, but LH release stimulated by LH-RH was also inhibited by inhibin in vitro. Using anti-porcine inhibin antibody and anti bovine inhibin antibody prepared by us, we could measure blood inhibin levels during rat, pig, cow and goat sexual cycles, human menstrual cycle, human pregnancy, and clomiphene-HMG stimulated menstrual cycle. We found maximum blood inhibin levels in the luteal phase and during pregnancy. These high levels of inhibin were demonstrated to be derived from the corpus luteum, pregnant corpus luteum and placenta. A diurnal rhythm of blood inhibin was demonstrated in men. In 1986 Vale et al. and Guillemin et al. demonstrated that homodimer and heterodimer of β-subunit of inhibin exist in the follicular fluid and have strong FSH-releasing action. These dimer of β-subunit were named FRP (FSH releasing protein)=Activin A and Activin AB, respectively. Since Erythroid Differentiation Factor (EDF) has the same chemical structure as Activin A, we demonstrated strong FSH releasing action of EDF in vivo as well as in vitro. We also found new three paracrine actions of activin. In conclusion, we demonstrated the control mechanism of FSH secretion from the pituitary is not so simple as that of LH secretion. LH secretion from the pituitary is controlled excusively by LH-RH. On the other hand, FSH secretion from the pituitary is stimulated by LH-RH, FSH-RH distinct from LH-RH, and activin, and is inhibited by inhibin. However, the chemical structure of FSH-RH distinct from LH-RH, and existence of activin in the hypothalamus and the peripheral blood remain to be elucidated.
社団法人日本産科婦人科学会の論文
1988-08-01

FSH分泌の調節機序

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