Altered secretion and processing of epidermal growth factor in adrenergic-induced growth of the rat submandibular gland.
The granular convoluted tubule (GCT) cells of the submandibular glands represent a major production site for epidermal growth factor (EGF). This study investigates EGF production in the submandibular glands in relation to beta-adrenergic stimulation. Rats were treated with isoproterenol (beta-agonist), which caused up to a 400% increase in submandibular tissue weight after 3 weeks. The weight increase coincided with marked morphologic changes, with degranulation and an apparent decrement in the number of the GCT cells. Immunostaining against EGF revealed a reduction in the number of EGF-immunoreactive cells. Concomitantly, the glandular contents of 6-kDa EGF decreased from 12.86+/-3.42 nmol/gland (mean+/-S.E.M.) in controls to 0.26+/-0.03 nmol/gland. EGF mRNA levels, expressed relative to total RNA levels, only tended to be reduced after 3 weeks as judged from RT-PCR and in situ hybridization (ISH). The isoproterenol-treated rats had increased output of EGF in the saliva, but the salivary secretion of protein was also increased. In both glandular tissue and saliva, gel filtration revealed partially processed high molecular weight forms of EGF in the isoproterenol-treated rats. These data indicate that isoproterenol treatment leads to a hyperstimulatory state of the GCT cells, which then causes depletion of the cellular stores of mature EGF, and most likely due to a shortened posttranslational transit, incomplete peptide processing.
Thulesen
Jesper
J
Department of Medical Anatomy, Section B, The Panum Institute, University of Copenhagen, Denmark. J.Thulesen@mai.ku.dk
Bor
Mustafa Vakur
MV
Thulesen
Stina
S
Nexø
Ebba
E
Poulsen
Steen Seier
SS
Jørgensen
Per Erik
PE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007545:Isoproterenol / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012463:Saliva / Q000737:chemistry; D013363:Submandibular Gland / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D007545:Isoproterenol