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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

Characterization of the proliferation of somatolactotropes from control and Zbtb20- mice.(a,b) Triple immunostaining of GH (red), PRL (green) and Ki67 (blue) was performed on the pituitaries from control and mutant mice at the indicated age. Arrowheads (a) indicate PRL+GH+ double-positive cells, which are Ki67 negative. Solid white arrows (b) indicate PRL+GH+ double-positive cells expressing Ki67, and open arrows (b) indicate PRL+GH- cells expressing Ki67. Scale bar, 25 μm. (c) The percentage of Ki67-expressing PRL+GH+ cells in PRL+GH+ cells was determined by counting serial sections of each pituitary at the indicated age. P3: n=22 sections from five animals; P4: n=19 sections from four animals; and P7: n=18 sections from four animals. Values represent mean±s.e.m. ND, not detectable.
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f5: Characterization of the proliferation of somatolactotropes from control and Zbtb20- mice.(a,b) Triple immunostaining of GH (red), PRL (green) and Ki67 (blue) was performed on the pituitaries from control and mutant mice at the indicated age. Arrowheads (a) indicate PRL+GH+ double-positive cells, which are Ki67 negative. Solid white arrows (b) indicate PRL+GH+ double-positive cells expressing Ki67, and open arrows (b) indicate PRL+GH- cells expressing Ki67. Scale bar, 25 μm. (c) The percentage of Ki67-expressing PRL+GH+ cells in PRL+GH+ cells was determined by counting serial sections of each pituitary at the indicated age. P3: n=22 sections from five animals; P4: n=19 sections from four animals; and P7: n=18 sections from four animals. Values represent mean±s.e.m. ND, not detectable.

Mentions: To evaluate the defect of lactotrope lineage expansion in the absence of ZBTB20 in more detail, we characterized somatolactotrope proliferation by triple immunostaining with the antibodies against GH, PRL and the cell proliferation marker Ki67. Unexpectedly, Ki67 expression was not detected in GH+/PRL+ cells from control mice until P4 (Fig. 5a,b), indicating a non-replicating state before P3. The Ki67-positive replicating somatolactotropes accounted for 6.5% (10/152) and 32.6% (30/92) of total GH+/PRL+ cells at P4 and P7 (Fig. 5c), respectively. Interestingly, Ki67 protein was also present in PRL+GH− cells in control pituitary at P7 and P14 (Fig. 5b). These data suggest that both somatolactotropes and differentiated lactotropes are normally proliferative, and may contribute to the lactotrope lineage expansion in pituitary development. In contrast, ZBTB20- somatolactotropes were consistently Ki67-negative, which transiently emerged before P3, and afterwards completely vanished before the entry into the time window of cell replication. Collectively, these data suggest that ZBTB20 is essential for the lineage specification and expansion of lactotropes.


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)

Characterization of the proliferation of somatolactotropes from control and Zbtb20- mice.(a,b) Triple immunostaining of GH (red), PRL (green) and Ki67 (blue) was performed on the pituitaries from control and mutant mice at the indicated age. Arrowheads (a) indicate PRL+GH+ double-positive cells, which are Ki67 negative. Solid white arrows (b) indicate PRL+GH+ double-positive cells expressing Ki67, and open arrows (b) indicate PRL+GH- cells expressing Ki67. Scale bar, 25 μm. (c) The percentage of Ki67-expressing PRL+GH+ cells in PRL+GH+ cells was determined by counting serial sections of each pituitary at the indicated age. P3: n=22 sections from five animals; P4: n=19 sections from four animals; and P7: n=18 sections from four animals. Values represent mean±s.e.m. ND, not detectable.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Characterization of the proliferation of somatolactotropes from control and Zbtb20- mice.(a,b) Triple immunostaining of GH (red), PRL (green) and Ki67 (blue) was performed on the pituitaries from control and mutant mice at the indicated age. Arrowheads (a) indicate PRL+GH+ double-positive cells, which are Ki67 negative. Solid white arrows (b) indicate PRL+GH+ double-positive cells expressing Ki67, and open arrows (b) indicate PRL+GH- cells expressing Ki67. Scale bar, 25 μm. (c) The percentage of Ki67-expressing PRL+GH+ cells in PRL+GH+ cells was determined by counting serial sections of each pituitary at the indicated age. P3: n=22 sections from five animals; P4: n=19 sections from four animals; and P7: n=18 sections from four animals. Values represent mean±s.e.m. ND, not detectable.
Mentions: To evaluate the defect of lactotrope lineage expansion in the absence of ZBTB20 in more detail, we characterized somatolactotrope proliferation by triple immunostaining with the antibodies against GH, PRL and the cell proliferation marker Ki67. Unexpectedly, Ki67 expression was not detected in GH+/PRL+ cells from control mice until P4 (Fig. 5a,b), indicating a non-replicating state before P3. The Ki67-positive replicating somatolactotropes accounted for 6.5% (10/152) and 32.6% (30/92) of total GH+/PRL+ cells at P4 and P7 (Fig. 5c), respectively. Interestingly, Ki67 protein was also present in PRL+GH− cells in control pituitary at P7 and P14 (Fig. 5b). These data suggest that both somatolactotropes and differentiated lactotropes are normally proliferative, and may contribute to the lactotrope lineage expansion in pituitary development. In contrast, ZBTB20- somatolactotropes were consistently Ki67-negative, which transiently emerged before P3, and afterwards completely vanished before the entry into the time window of cell replication. Collectively, these data suggest that ZBTB20 is essential for the lineage specification and expansion of lactotropes.

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