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ZBTB20 is required for anterior pituitary development and lactotrope specification.

Cao D, Ma X, Cai J, Luan J, Liu AJ, Yang R, Cao Y, Zhu X, Zhang H, Chen YX, Shi Y, Shi GX, Zou D, Cao X, Grusby MJ, Xie Z, Zhang WJ - Nat Commun (2016)

Bottom Line: Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes.Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ.In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.

ABSTRACT
The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20- mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

No MeSH data available.


Related in: MedlinePlus

Expression of ZBTB20 in the developing hypothalamus and pituitary.(a) ZBTB20 expression was detected by immunohistochemical staining at the indicated age on mouse adenohypophysis. White outline indicates adenohypophysis in embryo. AL, anterior lobe; IL, intermediate lobe; PL, posterior lobe. Scale bar, 200 μm. (b,c) Immunohistochemical double staining of ZBTB20 (red) and hormones (green) in pituitary at the indicated age. Inserts are enlargement of the framed areas. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts). (d) Triple staining of ZBTB20 (blue), PRL (green) and GH (red) in the pituitary at the indicated age. Arrowheads indicate PRL and GH double-positive cells expressing ZBTB20. Inserts show higher magnification of the area indicated by the arrowhead. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts).
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f7: Expression of ZBTB20 in the developing hypothalamus and pituitary.(a) ZBTB20 expression was detected by immunohistochemical staining at the indicated age on mouse adenohypophysis. White outline indicates adenohypophysis in embryo. AL, anterior lobe; IL, intermediate lobe; PL, posterior lobe. Scale bar, 200 μm. (b,c) Immunohistochemical double staining of ZBTB20 (red) and hormones (green) in pituitary at the indicated age. Inserts are enlargement of the framed areas. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts). (d) Triple staining of ZBTB20 (blue), PRL (green) and GH (red) in the pituitary at the indicated age. Arrowheads indicate PRL and GH double-positive cells expressing ZBTB20. Inserts show higher magnification of the area indicated by the arrowhead. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts).

Mentions: To understand the mechanisms by which ZBTB20 regulates anterior pituitary development and lactotrope specification, we examined its expression pattern in the developing pituitary and hypothalamus. The expression of ZBTB20 protein was first detected in hypothalamus as early as E13.5, but was excluded in pituitary at this time point (Supplementary Fig. 9). At E14.5, ZBTB20 protein was first detected in some cells of anterior pituitary, but absent in intermediate lobe (Fig. 7a). The number of ZBTB20-positive cells and intensity of ZBTB20 expression rapidly increased in the following 2 days. At E16.5, ZBTB20-positive cells were abundantly distributed over the entire anterior lobe, the expression levels of which were variable and much lower than hypothalamus. At P21, ZBTB20 expression was maintained at high levels in the pituitary (Fig. 7a). Double immunostaining of ZBTB20 and the pituitary hormones revealed that ZBTB20 was expressed by all the five endocrine cell types in anterior pituitary at P21 (Fig. 7b). Of note, most PRL-positive cells consistently expressed high levels of ZBTB20 from P0 to P14 (Fig. 7c). Furthermore, triple immunostaining with anti-GH, anti-PRL, and anti-ZBTB20 antibodies revealed high expression of ZBTB20 in somatolactotropes at both E18.5 and P4 (Fig. 7d). These data suggest that ZBTB20 might regulate anterior pituitary development and lactotrope specification in cell-autonomous and/or nonautonomous manners.


ZBTB20 is required for anterior pituitary development and lactotrope specification.

Cao D, Ma X, Cai J, Luan J, Liu AJ, Yang R, Cao Y, Zhu X, Zhang H, Chen YX, Shi Y, Shi GX, Zou D, Cao X, Grusby MJ, Xie Z, Zhang WJ - Nat Commun (2016)

Expression of ZBTB20 in the developing hypothalamus and pituitary.(a) ZBTB20 expression was detected by immunohistochemical staining at the indicated age on mouse adenohypophysis. White outline indicates adenohypophysis in embryo. AL, anterior lobe; IL, intermediate lobe; PL, posterior lobe. Scale bar, 200 μm. (b,c) Immunohistochemical double staining of ZBTB20 (red) and hormones (green) in pituitary at the indicated age. Inserts are enlargement of the framed areas. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts). (d) Triple staining of ZBTB20 (blue), PRL (green) and GH (red) in the pituitary at the indicated age. Arrowheads indicate PRL and GH double-positive cells expressing ZBTB20. Inserts show higher magnification of the area indicated by the arrowhead. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4835541&req=5

f7: Expression of ZBTB20 in the developing hypothalamus and pituitary.(a) ZBTB20 expression was detected by immunohistochemical staining at the indicated age on mouse adenohypophysis. White outline indicates adenohypophysis in embryo. AL, anterior lobe; IL, intermediate lobe; PL, posterior lobe. Scale bar, 200 μm. (b,c) Immunohistochemical double staining of ZBTB20 (red) and hormones (green) in pituitary at the indicated age. Inserts are enlargement of the framed areas. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts). (d) Triple staining of ZBTB20 (blue), PRL (green) and GH (red) in the pituitary at the indicated age. Arrowheads indicate PRL and GH double-positive cells expressing ZBTB20. Inserts show higher magnification of the area indicated by the arrowhead. Scale bar, 30 μm (outside the inserts); 10 μm (inside the inserts).
Mentions: To understand the mechanisms by which ZBTB20 regulates anterior pituitary development and lactotrope specification, we examined its expression pattern in the developing pituitary and hypothalamus. The expression of ZBTB20 protein was first detected in hypothalamus as early as E13.5, but was excluded in pituitary at this time point (Supplementary Fig. 9). At E14.5, ZBTB20 protein was first detected in some cells of anterior pituitary, but absent in intermediate lobe (Fig. 7a). The number of ZBTB20-positive cells and intensity of ZBTB20 expression rapidly increased in the following 2 days. At E16.5, ZBTB20-positive cells were abundantly distributed over the entire anterior lobe, the expression levels of which were variable and much lower than hypothalamus. At P21, ZBTB20 expression was maintained at high levels in the pituitary (Fig. 7a). Double immunostaining of ZBTB20 and the pituitary hormones revealed that ZBTB20 was expressed by all the five endocrine cell types in anterior pituitary at P21 (Fig. 7b). Of note, most PRL-positive cells consistently expressed high levels of ZBTB20 from P0 to P14 (Fig. 7c). Furthermore, triple immunostaining with anti-GH, anti-PRL, and anti-ZBTB20 antibodies revealed high expression of ZBTB20 in somatolactotropes at both E18.5 and P4 (Fig. 7d). These data suggest that ZBTB20 might regulate anterior pituitary development and lactotrope specification in cell-autonomous and/or nonautonomous manners.

Bottom Line: Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes.Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ.In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.

ABSTRACT
The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20- mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

No MeSH data available.


Related in: MedlinePlus