Immunohistochemical Localization of the Growth Hormone in Human Endometrium and Decidua

Sbracia, Marco; Scarpellini, F.; Poverini, R; Alò, Piero Luigi; Rossi, Gabriele; Tondo, U. Di

doi:10.1046/j.8755-8920.2003.00127.x

Cited by 34 publications

(30 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this regard it is interesting that uterine endometrium displays altered telomerase activity in a menstrual cycle-dependent manner despite its somatic origin (41). hGH has also been detected in endometrial epithelial cells (39). Thus, it may be possible that autocrine hGH participates in the regulation of telomerase activity required for temporal specific or cyclical proliferative activity.…”

Section: Discussionmentioning

confidence: 99%

αCP1 Mediates Stabilization of hTERT mRNA by Autocrine Human Growth Hormone

Emerald

Chen

Zhu

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

We herein demonstrate that autocrine human growth hormone production in human mammary carcinoma cells results in increased telomerase activity as a result of specific up-regulation of telomerase catalytic subunit (human telomerase reverse transcriptase (hTERT)) mRNA and protein. This increase in hTERT gene expression is not due to increased transcriptional activation of the hTERT promoter but is the result of increased stability of hTERT mRNA exerted by CU-rich cis-regulatory sequences present in the 3-untranslated region of TERT mRNA. Autocrine human growth hormone up-regulates two poly(C)-binding proteins, ␣CP1 and ␣CP2, which bind to these cis-regulatory elements and stabilize hTERT mRNA. We have therefore demonstrated that post-transcriptional modulation of the level of hTERT mRNA is one mechanism for regulation of cellular telomerase activity.Chromosomal ends consist of small DNA repeats that are not duplicated faithfully during replication resulting in loss of DNA during each replication. To faithfully replicate chromosomal ends, cells use a reverse transcriptase holoenzyme termed the telomerase complex (1). The template human telomerase RNA (hTR) 3 and the reverse transcriptase catalytic subunit (hTERT) are considered to be the major components of the human telomerase complex, because the expression of hTERT and hTR alone is able to restore the majority of telomerase activity (2). Telomerase activity is subject to stringent regulation and is regulated by multiple mechanisms such as hTERT mRNA transcription (3), splicing and maturation (4), protein phosphorylation and transport (5), and subcellular localization of each component of the telomerase complex (6). Telomerase activity is minimal in most somatic cells resulting in chromosome shortening after each proliferative cycle eventually resulting in crisis and cell death (7). However, telomerase activity is readily detected in 90% of all tumor cells (8), in all tissues during early development (9), and in tissues with continuous proliferation, such as the hematopoietic system or the epidermis (10, 11).mRNA turnover is one important mechanism by which gene expression is regulated (13). Specific interactions between sequences within the mRNA (cis-acting regulatory elements) and cellular RNA-binding proteins (trans-acting factors) regulate ribonuclease action and subsequent mRNA decay rates. The majority of these cis-acting elements are present in the 3Ј-untranslated region (3Ј-UTR) of the mRNA. cis-Regulatory elements such as AU-rich elements (12), Iron-responsive element (14), and CU-rich elements (15) within the 3Ј-UTR have been demonstrated to possess a role in mRNA stability. ␣-Globin mRNA poly(C)-rich segment-binding proteins (␣CPs), also referred to as poly(C)-binding proteins, and hnRNP K bind to CU-rich cis-regulatory elements (16). Two of the five members of poly(C)-binding proteins, ␣CP1 and ␣CP2, are highly homologous (16). Both ␣CP1 and ␣CP2 bind to pyrimidinerich elements in the 3Ј-UTR and stabilize a variety of mRNAs including ␣-globin and eryt...

show abstract

Section: Discussionmentioning

confidence: 99%

αCP1 Mediates Stabilization of hTERT mRNA by Autocrine Human Growth Hormone

Emerald

Chen

Zhu

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…GHR and GHR mRNA are also present in the uterus, including glandular and stromal cells [111][112][113], the decidua [114], and myometrium [111]. It is therefore possible that GH may act in an autocrine or paracrine way to regulate uterine growth or function.…”

Section: Uterine Tissuementioning

confidence: 99%

Extrapituitary growth hormone

Harvey

2010

Endocr

108

View full text Add to dashboard Cite

Pituitary somatotrophs secrete growth hormone (GH) into the bloodstream, to act as a hormone at receptor sites in most, if not all, tissues. These endocrine actions of circulating GH are abolished after pituitary ablation or hypophysectomy, indicating its pituitary source. GH gene expression is, however, not confined to the pituitary gland, as it occurs in neural, immune, reproductive, alimentary, and respiratory tissues and in the integumentary, muscular, skeletal, and cardiovascular systems, in which GH may act locally rather than as an endocrine. These actions are likely to be involved in the proliferation and differentiation of cells and tissues prior to the ontogeny of the pituitary gland. They are also likely to complement the endocrine actions of GH and are likely to maintain them after pituitary senescence and the somatopause. Autocrine or paracrine actions of GH are, however, sometimes mediated through different signaling mechanisms to those mediating its endocrine actions and these may promote oncogenesis. Extrapituitary GH may thus be of physiological and pathophysiological significance.

show abstract

“…hGH is also synthesized and functions locally within extrapituitary sites such as the mammary gland and endometrium (5). hGH is reported to be synthesized in the endometrial luminal epithelial cells during the mid to late luteal phase of the menstrual cycle (6). Slater et al (7) reported the increased expression of hGH in the endometrial epithelium-derived cells in both endometriosis and endometrioid adenocarcinoma.…”

mentioning

confidence: 99%

STAT3α Is Oncogenic for Endometrial Carcinoma Cells and Mediates the Oncogenic Effects of Autocrine Human Growth Hormone

et al. 2010

View full text Add to dashboard Cite

We herein demonstrate an oncogenic role for signal transducer and activator of transcription (STAT)-3alpha (the full length STAT3 isoform), which also mediates autocrine human GH (hGH)-stimulated oncogenicity, in human endometrial carcinoma (EC) cells. Autocrine hGH stimulated Y705 phosphorylation of STAT3 and STAT3-mediated transcriptional activity in a SRC and Janus-2 Kinase dependent manner in human EC cell lines. Forced expression of a constitutively active variant of STAT3alpha increased proliferation, anchorage-independent, three-dimensional (3D) Matrigel, and xenograft growth and promoted epithelial-mesenchymal transition, migration, and invasion of EC cells. Conversely, the oncogenic capacity of EC cells was significantly impaired by treatment with JSI-124, an inhibitor of STAT3 phosphorylation and activity, small interfering RNA-mediated depletion of STAT3alpha, or a dominant-negative variant of STAT3alpha. Furthermore, the enhanced EC cell oncogenicity stimulated by autocrine hGH, was also abrogated by functional inhibition or small interfering RNA-mediated depletion of STAT3alpha. STAT3alpha may therefore be a common mediator of oncogenic signaling pathways stimulating progression of EC.

show abstract

Immunohistochemical Localization of the Growth Hormone in Human Endometrium and Decidua

Abstract: The glandular cells of the human endometrium express GH from the late luteal phase throughout pregnancy in the decidual tissue. We suppose that GH plays an important role in blastocyst implantation.

Cited by 34 publications

References 25 publications

αCP1 Mediates Stabilization of hTERT mRNA by Autocrine Human Growth Hormone

αCP1 Mediates Stabilization of hTERT mRNA by Autocrine Human Growth Hormone

Extrapituitary growth hormone

STAT3α Is Oncogenic for Endometrial Carcinoma Cells and Mediates the Oncogenic Effects of Autocrine Human Growth Hormone

Contact Info

Product

Resources

About