Degradation of gonadotropin beta-subunits retained in the endoplasmic reticulum of the gonadotropes of castrated rats.
LH and FSH are composed of a common alpha-subunit and a noncovalently associated hormone-specific beta-subunit. Unassociated beta LH and beta FSH can be retained in the cisternae of endoplasmic reticulum (ER). This phenomenon is particularly evident in gonadotropes of castrated animals where beta-subunits are expressed in larger amounts than the alpha-subunit. Because little was known about the fate of the gonadotropin beta-subunits retained in the ER, we carried out immunocytochemical studies on ultrathin frozen sections of anterior pituitaries of castrated rats. After castration, the intracellular levels of the beta-subunits were found to increase more than that of the alpha-subunit. When the subcellular localization of the alpha- and beta-subunits and secretogranin II (a regulated secretory protein present in the secretory granules of gonadotropes of many species) was investigated by double immunoelectron microscopy, both gonadotropin subunits were colocalized in secretory granules with secretogranin II. However, only the beta-subunits, not the alpha-subunit and secretogranin II, were localized in the dilated cisternae of the ER as well as in irregularly shaped vacuoles. Using markers for the endoplasmic reticulum, the prelysosomal compartment and lysosomes (cathepsin D and lgp120), we found that these vacuoles correspond to a degradative compartment with two types of intermediates: 1) one with small amounts of lgp120, and cathepsin D preferentially localized at the periphery of a central dense matrix; and 2) the other with larger amounts of lgp120, and cathepsin D present all over the matrix of the vacuole. These vacuoles do not derive from autophagy because vesicles surrounded by a double or multilamellar membrane containing profiles of ER cisternae together with small amounts of the cytoplasm were never detected. Moreover, they do not correspond to crinophagic bodies because the latter contained beta-subunits as well as alpha-subunit and SgII. Our data indicate that gonadotropin beta-subunits, probably retained as unassociated subunits in the endoplasmic reticulum of castrated rat gonadotropes, undergo degradation in vacuoles that acquire lysosomal enzymes. This process appears different from the classical autophagy, but similar to the nonautophagic pathway for the diversion to lysosomes of the intracisternal granules accumulated in the ER of hyperstimulated thyrotropes.
Bassetti
M
M
Department of Medical Pharmacology, University of Milan, Italy.
Pasini
D L
DL
Rosa
P
P
D000818:Animals; D015415:Biomarkers; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D037201:Follicle Stimulating Hormone, beta Subunit; D006062:Gonadotropins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D015415:Biomarkers; D037201:Follicle Stimulating Hormone, beta Subunit; D006062:Gonadotropins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone