Homeobox genes in melatonin‐producing pinealocytes: Otx2 and Crx act to promote hormone synthesis in the mature rat pineal gland

Feb 26, 2019Journal of pineal research

Otx2 and Crx genes help boost melatonin production in mature rat pineal gland cells

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Abstract

Knocking down Otx2 and Crx together resulted in a significant reduction in melatonin-producing enzyme levels and melatonin release.

OTX2 and CRX are present exclusively in melatonin-producing cells of the rat pineal gland.
Targeted reduction of Otx2 decreased the expression of enzymes that synthesize melatonin.
A similar decrease in melatonin synthesis was observed with the reduction of Crx.
Simultaneous knockdown of both Otx2 and Crx led to an even greater reduction in melatonin synthesis and release.
These findings indicate that Otx2 and Crx may control the synthesis of melatonin in the mature pineal gland.

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Homeobox genes encode transcription factors that regulate developmental processes; however, in the pineal gland, a neuroendocrine organ responsible for nocturnal melatonin synthesis, expression of the homeobox genes Otx2 (orthodenticle homeobox 2) and Crx (cone-rod homeobox) persists postnatally. We here show that OTX2 and CRX are exclusively present in melatonin-producing pinealocytes of the rat pineal gland. To understand the roles of Otx2 and Crx in the mature pineal gland, we used siRNA technology in cultured rat pinealocytes with the nocturnal situation mimicked by adding norepinephrine to the culture media. siRNA-induced knockdown of Otx2 was found to reduce expression levels of the enzymes involved in melatonin synthesis at both transcript and protein levels. Similar results were obtained when knocking down Crx. Knocking down Otx2 and Crx simultaneously produced an even larger reduction in both transcript and protein levels of the melatonin-producing enzymes and also reduced the levels of melatonin released to the culture media. These results suggest that Otx2 and Crx, both alone and in combination, act to control pineal melatonin synthesis.

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Homeobox genes in melatonin‐producing pinealocytes: Otx2 and Crx act to promote hormone synthesis in the mature rat pineal gland

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