Regulation of sialomucin complex/Muc4 in the female rat reproductive tract

Sialomucin complex (SMC/rat Muc4) is a heterodimeric glycoprotein complex c omposed of an anti-adhesive mucin subunit ascites sialoglycoprotein (ASGP)- 1 and a transmembrane subunit ASGP-2. SMC expression is tightly regulated i n the uterus, and its expression appears to block blastocyst implantation. Expression is controlled by steroid hormone levels in the uterine luminal e pithelium, but not the uterine glandular epithelium, oviduct, cervix or vag ina. Increased progesterone levels lead to downregulation of SMC in the ute rine luminal epithelium at the time of receptivity for implantation. Transf orming growth factor beta (TGF-beta) has been implicated as a factor in ute rine progesterone responses. Studies on primary rat uterine luminal epithel ial cells showed that both SMC protein and transcript are downregulated by TGF-beta1, although SMC expression is not altered by treatments with oestro gen or progesterone, SMC is also downregulated when epithelial cells are co -cultured with isolated uterine stromal cells. Oestradiol and anti-TGF-beta block the stromal cell effect. These data indicate that uterine epithelial cells respond to hormones to downregulate SMC via an indirect effect on st romal cells involving paracrine action of TGF-beta.