title: PDIp is a major intracellular oestrogen-storage protein that modulates tissue levels of oestrogen in the pancreas.
abstract: E(2) (17β-oestradiol), a female sex hormone, has important biological functions in a woman's body. The pancreas, often considered a non-classical E(2)-targeting organ, is known to be functionally regulated by E(2), but little is known about how oestrogen actions are regulated in this organ. In the present study we report that PDIp (pancreas-specific protein disulfide isomerase), a protein-folding catalyst, can act as a major intracellular E(2) storage protein in a rat model to modulate the pancreatic tissue level, metabolism and action of E(2). The purified endogenous PDIp from both rat and human pancreatic tissues can bind E(2) with a K(d) value of approximately 150 nM. The endogenous PDIp-bound E(2) accounts for over 80% of the total protein-bound E(2) present in rat and human pancreatic tissues, and this binding protects E(2) from metabolic disposition and prolongs its duration of action. Importantly, we showed in ovariectomized female rats that the E(2) level in the pancreas reaches its highest level (9-fold increase over its basal level) at 24-48 h after a single injection of E(2), and even at 96 h its level is still approximately 5-fold higher. In contrast, the E(2) level in the uterus quickly returns to its basal level at 48 h after reaching its maximal level (approximately 2-fold increase) at 24 h. Taken together, these results show for the first time that PDIp is a predominant intracellular oestrogen storage protein in the pancreas, which offers novel mechanistic insights into the accumulation and action of oestrogen inside pancreatic cells.
authors: Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Xinmiao
authors: X
authors: Fu
authors: Pan
authors: P
authors: Wang
authors: Masayuki
authors: M
authors: Fukui
authors: Cheng
authors: C
authors: Long
authors: Linxiang
authors: L
authors: Yin
authors: Hye Joung
authors: HJ
authors: Choi
authors: Bao Ting
authors: BT
authors: Zhu
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D010179:Pancreas / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004967:Estrogens; D004958:Estradiol; D019704:Protein Disulfide-Isomerases