Beta cell mass regulation in the rat pancreas through glucocorticoids and thyroid hormones.
OBJECTIVE
To compare the effects of glucocorticoids and thyroid hormones on the regulation of the beta cell mass in the pancreas, the rats were treated and analyzed for cell cycle changes in islet and duct cells as a source for beta cell neogenesis.


METHODS
Different rat pancreases were morphometrically analyzed after immunohistochemical staining for markers of proliferation and apoptosis.


RESULTS
Hydrocortisone increased the beta cell mass of rat pancreases through an increase of proliferation. This effect was counteracted by an increase of apoptosis. In contrast, thyroxine decreased the beta cell mass through an increase of apoptosis. This effect was counteracted by an increased rate of proliferation. Combined treatment with both hormones nullified the antagonistic effects on proliferation, apoptosis, and beta cell mass, thereby contributing to the maintenance of a stable total beta cell volume of the pancreas.


CONCLUSIONS
Hydrocortisone and thyroxine induced analogous changes in pancreatic duct cells, which represent a crucial pool for new beta cells through neogenesis. This may explain the positive effects of glucocorticoids in the immunosuppressive therapy regimen after whole pancreas transplantation upon long-term insulin independence, which is not achievable with isolated islets because of the loss of duct cells during the islet process before transplantation.
Jörns
Anne
A
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany. Joerns.Anne@mh-hannover.de
Sennholz
Christoph
C
Naujok
Ortwin
O
Lenzen
Sigurd
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism
D005938:Glucocorticoids; D018398:Homeodomain Proteins; D013963:Thyroid Hormones; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D001973:Bromodeoxyuridine; D013974:Thyroxine; D006854:Hydrocortisone