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Occurrence and nuclear localization of cAMP response element-binding protein in the post-natal development of the rat
Insights
Cyclic AMP response element-binding protein (CREB) is crucial for rat submandibular gland development. It regulates both acinar cell growth and duct cell differentiation, particularly in granular convoluted tubule formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Biology
Background:
- Cyclic AMP response element-binding protein (CREB) is a transcription factor regulating gene expression.
- The submandibular gland undergoes significant postnatal development involving acinar and ductal cell differentiation.
- Understanding CREB's role is key to deciphering gland morphogenesis.
Purpose of the Study:
- To investigate the spatiotemporal distribution of CREB during postnatal rat submandibular gland development.
- To explore CREB's involvement in acinar cell growth and ductal cell differentiation.
- To examine CREB's role in the androgen-regulated differentiation of granular convoluted tubules.
Main Methods:
- Immunohistochemistry was used to detect CREB expression in rat submandibular glands at various postnatal ages.
- Beta-adrenergic agonist (isoproterenol) and testosterone administration were employed to study CREB regulation.
- Analysis focused on nuclear CREB immunoreactivity in acinar and ductal cells.
Main Results:
- CREB expression shifted from moderate in newborn tubule/duct cells to intense in acinar cells by 1-2 weeks.
- Isoproterenol treatment transiently increased CREB-positive acinar cells.
- Post-3 weeks, CREB localized to intercalated and striated duct cells, preceding granular convoluted tubule formation. Testosterone induced CREB in duct cells, leading to differentiation.
Conclusions:
- CREB plays a vital role in both beta-adrenergic regulated acinar cell development and duct system differentiation.
- CREB is particularly important for androgen-induced differentiation of granular convoluted tubular cells.
- These findings highlight CREB's multifaceted involvement in submandibular gland morphogenesis.
Abstract:
Cyclic AMP response element-binding protein (CREB) is a 43-kDa polypeptide that binds a cAMP response element located at the 5' promoter region of cAMP regulatory genes. The spatial and temporal distribution of CREB in the postnatal development of the rat submandibular gland was investigated using immunohistochemistry with a specific antibody. At birth, cells of the terminal tubules and ducts in the submandibular gland showed a nuclear CREB immunoreactivity of moderate intensity. At 1-2 weeks after birth, an intense CREB immunoreactivity was localized primarily to acinar cells. When the beta-adrenergic agonist isoproterenol was administered to 2-week-old rats, a twofold transient increase in the number of immunoreactive acinar cells was induced. Beginning 3 weeks after birth, CREB immunoreactivity shifted from acini to the duct system and showed a clear localization in the cells of the intercalated ducts and distal portions of striated ducts, where the granular convoluted tubule develops after 4 weeks. Immunopositive materials were localized exclusively in the nuclei of both acinar and ductal immunoreactive cells. After the development of the granular convoluted tubules, CREB immunoreactivity was absent in the tubule cells and was gradually reduced in intensity over the entire gland. In order to examine a hypothesis that CREB is involved in the initial differentiation of the granular convoluted tubular cells, testosterone was administered to hypophysectomized adult rats. Whereas the tubular cells of hypophysectomized rats showed a complete regression, and no CREB immunoreactivity was found in any acinar or duct cells, administration of testosterone for a few days induced an intense CREB immunoreactivity in the nuclei of duct cells, followed by their differentiation into the granular convoluted tubular cells. These results suggested that CREB is involved not only in the growth and differentiation of acinar cells that are regulated by beta-adrenergic nerves but also in those of the duct system, and especially in the androgen-regulated differentiation of the granular convoluted tubular cells, during the post-natal development of the rat submandibular gland.