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Ontogenesis of proopiomelanocortin gene expression and regulation in the rat pituitary intermediate lobe
C Hindelang1, J M Félix, F M Laurent
1Institut de Physiologie, URA CNRS 309, Strasbourg, France.
Abstract:
During ontogenesis, proopiomelanocortin (POMC) mRNA appears in the pituitary intermediate lobe (IL) at embryonic day 16 (E16), rather later than in the hypothalamic arcuate nucleus (E13) or the pituitary anterior lobe (E15). POMC mRNA onset in the IL correlates with the appearance of POMC-derived peptides detected by immunocytochemistry (ICC), indicating that there is probably no time lag between POMC mRNA translation. Subsequently, while the IL lobular organization developed progressively, the number of in situ hybridization- (ISH) and ICC-positive cells increased until after birth. During postnatal development, coinciding with innervation of the IL, the POMC mRNA level in the lobe, measured by quantitative ISH, increased about 4-fold to reach the adult value at weaning. The effects of acute or chronic postnatal treatment with a dopamine antagonist (haloperidol) or a dopamine agonist (bromocriptine) show that the physiological dopaminergic inhibitory control of POMC gene expression operates as early as postnatal day 5. The subsequent increase in mRNA levels despite the inhibitory innervation raises the question of the existence of some unknown positive regulation active during postnatal development.
Insights
Proopiomelanocortin (POMC) gene expression in the pituitary intermediate lobe begins late in development. Dopaminergic inhibition is active early, but unknown positive regulation may drive later increases in POMC mRNA.
Area of Science:
- Neuroendocrinology
- Developmental Biology
- Molecular Endocrinology
Background:
- Proopiomelanocortin (POMC) is a key precursor peptide in the pituitary.
- POMC expression timing and regulation during development are not fully understood.
Purpose of the Study:
- To investigate the ontogeny of POMC mRNA expression in the pituitary intermediate lobe (IL).
- To determine the onset and developmental changes in POMC gene expression and its regulation.
Main Methods:
- In situ hybridization (ISH) for POMC mRNA detection.
- Immunocytochemistry (ICC) for POMC-derived peptides.
- Quantitative analysis of POMC mRNA levels.
- Pharmacological manipulation with dopamine agonists/antagonists.
Main Results:
- POMC mRNA appears in the IL at embryonic day 16, later than in other pituitary regions.
- Expression onset correlates with peptide detection, suggesting no translation lag.
- POMC mRNA levels increase postnatally, coinciding with innervation.
- Dopaminergic inhibitory control is functional by postnatal day 5.
Conclusions:
- POMC gene expression in the IL follows a specific developmental timeline.
- Early postnatal dopaminergic inhibition of POMC is established.
- A potential unknown positive regulatory mechanism may influence postnatal POMC mRNA accumulation.