Estradiol alleviates acinar cell apoptosis and chronic pancreatitis in male Wistar Bonn/Kobori rats.

Abstract

AIMS:

To quantitatively determine the influence of estradiol on acinar cell apoptosis and chronic pancreatitis; assess its effects on infiltration of CD4 and CD8 T cells in the pancreas; investigate the role of testosterone on chronic pancreatitis in 20-week-old male WBN/Kob rats; and determine the impact of estradiol on proliferation of splenocytes derived from these animals in vitro.

METHODOLOGY AND FINDINGS:

Treatment with high (0.4 mg x kg x week) but not low (0.1 mg x kg x week) doses of estradiol for 10 weeks significantly decreased the number of apoptotic acinar cells stained with an anti-single strand DNA antibody, histologic scores, and pancreatic myeloperoxidase activity in 20-week-old WBN/Kob rats, in comparison with control values. The high doses also significantly attenuated the increase in pancreatic hydroxyproline content, an indicator of collagen deposition, at 20 weeks. They caused significant decreases in the numbers of CD4 and CD8 T cells infiltrating the pancreas. Both doses suppressed levels of testosterone but without any influence on the serum corticosterone concentrations. Androgen receptors could not be immunohistochemically identified in the pancreas at 20 weeks, and dietary treatment with flutamide, an androgen receptor antagonist, did not influence the chronic pancreatitis. Estradiol significantly reduced 1% phytohemagglutinin-induced incorporation of bromodeoxyuridine into the splenocytes in vitro.

CONCLUSIONS:

We conclude that estradiol dose-dependently attenuates acinar cell apoptosis and development of chronic pancreatitis, independent of any change in endogenous corticosterone and testosterone, by suppressing infiltration and function of T cells.

• Authors: Soichi Nakamura, Tamaki Yamada, Takashi Hashimoto, Satoru Takahashi, Mitsue Sogawa, Hirotaka Ohara, Takahiro Nakazawa, Hitoshi Sano, Atsushi Kuno, Takashi Joh, Tomoyuki Nomura, Tetsuo Arakawa, Makoto Itoh
• Journal: Pancreas (Pancreas) Vol. 26 Issue 3 Pg. e59-66 (Apr 2003) ISSN: 1536-4828 [Electronic] United States
• PMID: 12657966 (Publication Type: Journal Article)

Chemical References

• Androgen Antagonists
• Hormones
• Receptors, Androgen
• Estradiol
• Flutamide
• Hydroxyproline

Topics

• Androgen Antagonists (therapeutic use)
• Animals
• Apoptosis (drug effects)
• Body Weight (drug effects)
• Cell Movement (drug effects)
• Chronic Disease
• Estradiol (blood, therapeutic use)
• Flutamide (therapeutic use)
• Hormones (blood)
• Hydroxyproline (analysis)
• Male
• Organ Size (drug effects)
• Pancreas (drug effects, immunology, pathology)
• Pancreatitis (drug therapy, immunology, pathology)
• Rats
• Rats, Inbred Strains
• Rats, Wistar
• Receptors, Androgen (analysis)
• Spleen (cytology, drug effects)
• T-Lymphocytes (drug effects, immunology)