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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH) and prolactin (PRL) are anterior pituitary hormones that have multiple roles in growth and metabolism. Both hormones are important in mammary development and breast cancer. The epidermal growth factor (EGF) family of peptides and the receptors that they activate (the ErbB family) are also major players in mammary biology and pathophysiology. Recent studies in signal transduction have highlighted the interplay between signaling pathways referred to as crosstalk. In this review, cell biological and signaling studies related to crosstalk between GH and PRL and the ErbB family are discussed. In particular, the role of GH- and PRL-induced phosphorylation of ErbB receptors in regulating EGF responsiveness is highlighted with attention to potential pathophysiological relevance.
J Mammary Gland Biol Neoplasia 2008 Mar
PMID:Mechanistic aspects of crosstalk between GH and PRL and ErbB receptor family signaling. 1823 42

Growth hormone (GH) deficiency and resultant growth failure are common sequelae in children with brain tumors, often requiring treatment with GH. Several studies over the past decade have addressed the concern as to whether GH treatment in these children results in an increased rate of tumor recurrence. The findings in general are reassuring, although there are analytic problems with all the studies. This present article reviews the previously published studies, as well as the experience at the Children's Hospital of Philadelphia.
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PMID:Is brain tumor recurrence increased following growth hormone treatment? 1840 3

Although the pubertal surge of estrogen is the immediate stimulus to mammary development, the action of estrogen depends upon the presence of pituitary growth hormone and the ability of GH to stimulate production of IGF-I in the mammary gland. Growth hormone binds to its receptor in the mammary fat pad, after which production of IGF-I mRNA and IGF-I protein occurs. It is likely that IGF-I then works through paracrine means to stimulate formation of TEBs, which then form ducts by bifurcating or trifurcating and extending through the mammary fat pad. By the time pubertal development is complete a tree-like structure of branching ducts fills the rodent mammary fat pad. In addition to requiring IGF-I in order to act, estradiol also directly synergizes with IGF-I to enhance formation of TEBs and ductal morphogenesis. Together they increase IRS-1 phosphorylation and cell proliferation, and inhibit apoptosis. In fact, the entire process of ductal morphogenesis, in oophorectomized IGF-I(-/-) knockout female mice, can occur as a result of the combined actions of estradiol and IGF-I. IGF-I also permits progesterone action in the mammary gland. Together they have been shown to stimulate a form of ductal morphogenesis, which is anatomically different from the kind induced by IGF-I and estradiol. Although both progesterone and estradiol synergize with IGF-I by increasing IGF-I action parameters, there must be other, as yet unknown mechanisms that account for the anatomical differences in the different forms of ductal morphogenesis observed (hyperplasia in response to IGF-I plus estradiol and single layered ducts in response to IGF-I plus progesterone).
J Mammary Gland Biol Neoplasia 2008 Dec
PMID:IGF-I, GH, and sex steroid effects in normal mammary gland development. 1903 33

Ectopic secretion of growth hormone-releasing-hormone (GHRH) is a rare cause of acromegaly-representing less than 1% of patients. A 25-year-old woman was admitted to the hospital with acromegaly and a 6 x 6 cm infrahepatic mass. Sellar magnetic resonance imaging indicated diffuse pituitary enlargement consistent with hyperplasia. The infrahepatic mass was resected, and the histopathological diagnosis was a well-differentiated invasive neuroendocrine carcinoma of the duodenum with metastases to local lymph nodes. The tumor cells contained cytoplasmic immunoreactivity for GHRH. Because increased IGF-1 concentrations persisted after the operation, the patient was treated with octreotide long-acting repeatable (LAR) injections of 20 mg/month. Growth hormone and IGF-1 levels normalized. After 6 years of surveillance, a left paraaortic mass was detected by uptake of indium 111 octreotide. Surgical exploration revealed metastatic neuroendocrine carcinoma in a 2.5-cm lymph node. Postoperatively, the IGF-1 concentration was mildly elevated. Octreotide LAR therapy is being continued at 10 mg/month. This case suggests that octreotide treatment may have a beneficial effect on disease course and can be maintained for as long as 7 years in a patient with acromegaly due to a GHRH-secreting neuroendocrine carcinoma.
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PMID:Ectopic growth hormone-releasing hormone secretion by a neuroendocrine tumor causing acromegaly: long-term follow-up results. 1930 Nov 54

Recent molecular pathological investigations have elucidated the cytodifferentiation of pituitary cells and identified several transcriptional factors that regulate this cytodifferentiation of pituitary cells. The patterns of cytodifferentiation are closely related to the pathogenesis of pituitary adenomas. Meanwhile, the role of hypothalamic hormones in the development of pituitary adenomas has recently attracted the attention of investigators. The expression of growth hormone-releasing hormone and corticotrophin releasing hormone in corticotroph adenomas have been demonstrated in somatotroph adenomas and corticotropin adenomas, respectively. This finding indicates that the endogenous expression of hypothalamic hormones and their receptors in human pituitary adenoma cells has ample significance in the autocrine or paracrine regulation of pituitary hormone production and tumor extension induced by hypothalamic hormones produced by adenoma cells. The recent progress in surgical techniques for treatment of pituitary adenomas has provided several alternatives: transsphenoidal surgery vs. transcranial surgery, sublabial approach vs. endonasal approach, and microsurgery vs. endoscopic surgery. There have also been developments in the medical treatment of pituitary adenomas. The frequently used dopamine agonist, cabergoline, is very effective for treating prolactin-producing adenoma. Long-acting octreotide and pegvisomant are now available for the treatment of growth hormone producing adenoma. Cabergoline is also used for growth hormone producing adenoma. Temozolomide has recently been used for atypical adenomas or pituitary carcinomas. Adult growth hormone deficiency sometimes occurs in postoperative patients with pituitary adenomas. Growth hormone replacement is recommended to maintain the quality of life of these patients.
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PMID:[Recent trends in the pathophysiology and treatment of pituitary adenomas]. 1969 85

Thyrotropin (thyroid-stimulating hormone (TSH))-producing pituitary adenomas have been known to be quite variable in clinical features covering from typical functioning TSH-producing adenomas (FTSHomas) associated with hyperthyroidism to clinically silent TSH cell adenomas (STAs) that are apparently unassociated with hyperthyroidism. It is important to distinguish STAs from other types of clinically non-functioning adenomas for adequate postoperative managements. However, because of rareness of TSH-producing adenomas, their histopathological features linking to the clinical manifestations have not been well characterized. Herein, we investigated clinical and histopathological findings to characterize 29 TSH-producing adenomas including 20 FTSHomas and nine STAs. Clinical symptoms of the patients with STAs included headache, visual defect, vertigo, and nausea. All STAs and 19 FTSHomas were macroadenoma. The average tumor size of STAs was significantly larger than that of FTSHomas (P < 0.05). The invasiveness was detected in 33% STAs and in 20% FTSHomas. Both STAs and FTSHomas showed a variety of morphological features and immunohistochemical profiles. Chromophobic polygonal or short-spindled tumor cells usually proliferated in a diffuse pattern, while they exhibited globoid or whorl-like appearance with intertwined cytoplasmic processes in both subgroups. Stromal fibrosis and calcification were often noted. Their nuclei were somehow pleomorphic. Ultrastructural features of all four STAs examined were similar to those of normal thyrotrophs. Thus, STAs and FTSHomas were indistinguishable by histology alone. Immunohistochemically, the number of TSH-positive cells in individual FTSHomas was highly various. Six tumors showed only a few TSH-positive cells (1-5%), and three were negative for TSH by conventional method without antigen retrieval. After proteinase K treatment, these tumors turned out TSH positive. As defined, STAs were TSH positive in more than 20% of tumor cells and three of them in more than 50%. Growth hormone- and/or prolactin-positive cells were detected in 55% STAs and 63% FTSHomas. Both pituitary-specific transcription factor 1 and GATA-binding protein 2 were expressed in all STAs and 20 FTSHomas. Membranous somatostatin receptor (SSTR)-2A immunoreactivity was found in 89% STAs and 94% FTSHomas, whereas SSTR5 was positive in 78% of both STAs and FTSHomas. MIB-1 labeling index was related to tumor invasiveness and tumor size (P < 0.05, P = 0.09, respectively). Thus, although both STAs and FTSHomas showed unique histopathological features distinct from other type adenomas, these two subgroups were indistinguishable by histopathology. Immunohistochemistry for TSH by use of antigen retrieval, transcription factors, and SSTRs may be useful to confirm STAs and to determine the postoperative therapy among various kinds of clinically non-functioning adenomas.
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PMID:Clinicopathological characterization of TSH-producing adenomas: special reference to TSH-immunoreactive but clinically non-functioning adenomas. 1977 99

Growth hormone (GH)-secreting pituitary adenomas represent a common source of GH excess in patients with acromegaly. Whereas surgical extirpation of the culprit lesion is considered first-line treatment, as many as 19% of patients develop recurrent symptoms due to regrowth of previously resected adenomatous tissue or to continued growth of the surgically inaccessible tumor. Although medical therapies that suppress GH production can be effective in the management of primary and recurrent acromegaly, these therapies are not curative, and lifelong treatment is required for hormonal control. Stereotactic radiosurgery has emerged as an effective adjunctive treatment modality, and is an appealing alternative to conventional fractionated radiation therapy. The authors reviewed the growing body of literature concerning the role of radiosurgical procedures in the treatment armamentarium of acromegaly, and identified more than 1350 patients across 45 case series. In this review, the authors report that radiosurgery offers true hormonal normalization in 17% to 82% of patients and tumor growth control in 37% to 100% of cases across all series, while minimizing adverse complications. As a result, stereotactic radiosurgery represents a safe and effective treatment option in the multimodal management of primary or recurrent acromegaly secondary to GH-secreting pituitary adenomas.
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PMID:The role of stereotactic radiosurgery in the multimodal management of growth hormone-secreting pituitary adenomas. 2088 21

Growth hormone (GH), insulin-like growth factor (IGF)-I and insulin have potent growth-promoting and anabolic actions. Their potential involvement in tumor promotion and progression has been of concern for several decades. The evidence that GH, IGF-I and insulin can promote and contribute to cancer progression comes from various sources, including transgenic and knockout mouse models and animal and human cell lines derived from cancers. Assessments of the GH-IGF axis in healthy individuals followed up to assess cancer incidence provide direct evidence of this risk; raised IGF-I levels in blood are associated with a slightly increased risk of some cancers. Studies of human diseases characterized by excess growth factor secretion or treated with growth factors have produced reassuring data, with no notable increases in de novo cancers in children treated with GH. Although follow-up for the vast majority of these children does not yet extend beyond young adulthood, a slight increase in cancers in those with long-standing excess GH secretion (as seen in patients with acromegaly) and no overall increase in cancer with insulin treatment, have been observed. Nevertheless, long-term surveillance for cancer incidence in all populations exposed to increased levels of GH is vitally important.
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PMID:Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. 2095 99

Growth hormone excess has been associated with hypercalciuria and nephrolithiasis. Hypercalcemia in acromegaly is rare and usually due to coexistent primary hyperparathyroidism. To report two cases of 1,25-dihydroxyvitamin D (1,25 (OH)(2) D)-dependent hypercalcemia in cromegaly. A 50 year-old female with 2 years history of hypercalcemia presented with features of acromegaly. Serum calcium (Ca) was 10.9 mg/dl (8.6-10.2), parathyroid hormone (PTH) 20 pg/ml (10-65), PTH-related peptide undetectable, and 1,25 (OH)(2) D 119 pg/ml (15-75). Insulin-like growth factor 1 (IGF1) was 911 ng/ml (49-292) and growth hormone (GH) 14.5 ng/ml (0.03-10). MRI showed a 1.7 cm pituitary tumor. Transsphenoidal adenectomy (TSA) resulted in normalization of IGF1, GH, Ca, and 1,25 (OH)(2) D (50 pg/ml) and complete tumor resection. A 52-year-old female was diagnosed with visual field deficits on routine exam. MRI showed a 3 cm invasive pituitary macroadenoma. IGF1 was 416 ng/ml (87-238) and GH 75.8 (0-6.0) ng/ml. Incidentally, she was found with high Ca of 10.8 mg/dl (8.9-10.3) associated with PTH 19 pg/ml and 1,25 (OH)(2) D66 pg/ml. Postoperatively, IGF1 and GH remained abnormal (440 and 12.8 ng/ml, respectively), while MRI showed parasellar tumor residue. Ca remained high (10.1-11.1 mg/dl), along with elevated 1,25 (OH)(2) D level (81.3 pg/ml). In both cases, other causes of hypercalcemia were ruled out. We present 2 cases of 1,25 (OH)(2) D-dependent hypercalcemia associated with growth hormone excess. Complete resection of tumor produced biochemical remission of acromegaly and normalization of calcium and 1,25 (OH)(2) D levels, while incomplete resection was associated with persistent 1,25 (OH)(2) D-dependent hypercalcemia. Acromegaly should be considered a cause of 1,25 (OH)(2) D-dependent hypercalcemia.
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PMID:Acromegaly as a cause of 1,25-dihydroxyvitamin D-dependent hypercalcemia: case reports and review of the literature. 2118 40

Growth hormone (GH) controls hepatic physiology to a large extent through the transcription factor signal transducers and activators of transcription (STAT) 5. Here, we focus on lessons learned from the physiology and pathophysiology of mice with disrupted Ghr and Stat5 loci. We discuss that hepatosteatosis and hepatocellular carcinoma observed in the absence of STAT5 can be explained in part through an aberrant activation of STAT1 and STAT3, which in themselves promote cell proliferation and survival. We also argue that STAT5 can be a context-specific tumor suppressor as it negatively regulates cell cycle progression. Lastly, we discuss promiscuity between STAT members that permits a given cytokine receptor to activate different STATs and thereby elicit context-dependent biological responses.
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PMID:Context-Specific Growth Hormone Signaling through the Transcription Factor STAT5: Implications for the Etiology of Hepatosteatosis and Hepatocellular Carcinoma. 2220 2


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