Betaglycan localization in the female rat pituitary: implications for the regulation of follicle-stimulating hormone by inhibin.
Activin-stimulated FSH synthesis and secretion from the pituitary gonadotrope is negatively modulated by ovarian inhibin; however, the cellular mechanism of inhibin antagonism is unknown. Inhibin and activin share a common beta-subunit through which inhibin can compete with activin for binding to the activin type II receptor and prevent activin signal transduction. Although the affinity of inhibin for binding to the activin receptor is far lower than that of activin itself, inhibin is capable of inhibiting activin-stimulated FSH synthesis and secretion even at low or equimolar concentrations. It is now known that the TGFbeta type III receptor, betaglycan, acts as an inhibin coreceptor that binds the inhibins and increases their affinity for the activin type II receptor, thereby enhancing the antagonistic effect of inhibin on activin signal transduction. Yet, despite the characterization of betaglycan is an inhibin coreceptor in several cell models in vitro, the role of this protein in the regulation of FSH in vivo has not been demonstrated. In this study we sought to understand more fully the function of betaglycan in the control of FSH release by the gonadotrope by describing betaglycan immunolocalization in the pituitary and assessing its correlation to fluctuations in FSH and inhibin throughout the rat estrous cycle. In general, betaglycan immunoreactivity was present in the anterior pituitary at all estrous cycle time points, but was confined to the membrane of gonadotropes just before and after the primary and secondary FSH surges. Importantly, betaglycan localized to the gonadotrope membrane when inhibin must rapidly reduce FSH to basal levels after the secondary FSH surge. These data indirectly support a role for betaglycan in vivo as a coreceptor that is required for inhibin-modulated FSH release from the pituitary.
D000818:Animals; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D007265:Inhibins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D007265:Inhibins; D005640:Follicle Stimulating Hormone