Disease relevance of GH

• In carcinomas GH mRNA was also found in progesterone receptor-negative tissue samples, indicating that after malignant transformation GH gene expression may become progestin independent [1].
• In conclusion, this Dalmatian dog with acromegaly and insulin resistance represents the first case of GH hypersecretion proven to be due to a somatotroph adenoma [2].
• The pituitary gland contained an acidophilic adenoma that immunostained positively for GH (and negatively for ACTH and alpha-MSH) [2].
• For these studies chimeric genes that encode hybrid proteins containing carboxy-terminal portions of the influenza virus hemagglutinin (154 amino acids) or the vesicular stomatitis virus envelope glycoprotein (G) (60 amino acids) linked to the carboxy terminus of a nearly complete secretory polypeptide, growth hormone (GH), were used [3].
• To determine the functional role of growth hormone (GH) secretagogue in myocardium with ischemia, left ventricular (LV) pressure gauge, wall thickness crystals, coronary occluder, pacers, and catheters were implanted in 26 dogs [4].

Psychiatry related information on GH

• Findings in this animal model are discussed within the context of noradrenergic-hypothalamic-GH dysfunction reported in some but not all types of anxiety disorders in humans [5].
• The plasma peptide YY, ghrelin, and growth hormone (GH) concentrations increased due to food deprivation, while the T4 and Acrp30 concentrations decreased [6].

High impact information on GH

• At present we demonstrate the expression of the gene encoding GH in the mammary gland of dogs and cats using reverse-transcriptase PCR [1].
• The demonstration of progestin-stimulated GH expression in mammary tissue of cats indicates that the phenomenon is more generalized among mammals [1].
• It is concluded that GH gene expression occurs in normal, hyperplastic, and neoplastic mammary tissue of the dog [1].
• Effectively, GH became part of the luminal segment of membrane proteins of which only very small segments, corresponding to the cytoplasmic portions of the G or HA proteins, remained exposed on the surface of the microsomes [3].
• The hybrid polypeptide containing the carboxy-terminal portion of HA linked to GH accumulated in a juxtanuclear region of the cytoplasm within modified ER cisternae, closely apposed to the Golgi apparatus [3].

Chemical compound and disease context of GH

• The growth hormone (GH) secretagogue activity of variable dosages of clonidine (16.5, 50, 150, and 450 micrograms/kg of body weight), given orally mixed with the daily food ration, was evaluated in young and old dogs [7].
• Other laboratory abnormalities included nonregenerative, normocytic, normochromic anemia; mild hypercalcemia; and an impaired growth hormone (GH) secretory response after xylazine administration [8].
• It is concluded that local production of GH is not involved in progestin-induced hyperplasia of uterine epithelial cells in dogs [9].
• Acromegaly associated soft tissue changes were also reversible after MPA withdrawal and/or OVx-HYx when GH levels had dropped [10].

Biological context of GH

• Among the negative samples were progestin-treated dogs with high mammary GH gene expression [11].
• We have characterized the canine mammary and pituitary GH gene transcripts by Northern blot, 5'- and 3'-RACE (rapid amplification of cDNA ends), and DNA sequence analysis [11].
• These findings indicate that mammary and pituitary GH gene transcripts originate from the same transcription start site but are regulated differentially [11].
• In addition, plasma GH profiles and plasma concentrations of IGF-I, IGF-II, and insulin-like growth factor-binding protein 4 and -6 (IGFBP-4 and -6) were measured to assess their potential systemic role during bone formation [12].
• The aim of the present study was to determine the expression of growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and bone morphogenetic protein 2 (BMP-2) in distraction-induced bone regeneration [12].

Anatomical context of GH

• Northern blot analysis detected GH gene transcripts in mammary glands of dogs which were exposed to high levels of progestins [11].
• Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA [13].
• GH was also associated with areas of hyperplastic mammary epithelium, which may indicate that locally produced GH enhances proliferation, acting in an autocrine and/or paracrine manner [13].
• Local synthesis of GH was also proven immunoelectron microscopically by demonstrating GH-containing secretory granules [13].
• In normal and HF myocytes, GH (0.4-40 x 10(-3) IU/ml) had no effect on either cell shortening or [Ca2+]i transients [14].

Associations of GH with chemical compounds

• In both age groups, the GHSs were specific for GH release as they did not cause significant elevations in the plasma concentrations of ACTH, cortisol, TSH, LH, and PRL [15].
• The basal serum growth hormone (GH) concentration was markedly elevated (23microg/l) and did not decrease during a glucose tolerance test or after somatostatin administration [2].
• In nonmalignant mammary tissues, GH production is stimulated by progesterone and synthetic progestins interacting with progesterone receptors [13].
• MK-0677, a spiroindoline sulfonamide, is a novel, orally active GH secretagogue [16].
• METHODS: To determine whether GH and IGF-1 have a direct effect on myocardial contractility and whether the GH/IGF-1-induced effect was the results of changes in Ca2+ activation, cell shortening and [Ca2+]i transient were simultaneously measured in the left ventricular myocyte preparations, isolated from normal and rapid pacing-induced HF dogs [14].

Regulatory relationships of GH

• Upregulation of GHR expression in distraction osteogenesis may enhance sensitivity to endogenous systemic GH and thus promote consolidation of the regenerated bone [12].

Other interactions of GH

• Pituitary GH gene expression is highly dependent upon the transcription factor Pit-1 [11].
• It is concluded that the activated PR may transactivate GH expression in the mammary gland within the same cell and functions as a pre-requisite transcription factor [17].
• Based on peak responses and total GH release, L-692,585 was 10- to 20-fold and 2- to 2.5-fold more potent than L-692,429 and the growth hormone releasing peptide, GHRP-6, respectively [18].
• The Na+-gradient Pi overshoot in vesicles isolated from normal, GH-treated and thyroparathyroidectomized dogs was increased after in vivo PTH administration [19].
• This study examined the effect of growth hormone (GH) on hepatic glucose metabolism and on the fractional extraction of insulin and glucagon after oral glucose administration [20].

Analytical, diagnostic and therapeutic context of GH

• Changes in the systemic osteotropic growth factors GH, IGF-I, IGF-II, IGFBP-4, and IGFBP-6 do not seem to be of importance during distraction osteogenesis [12].
• After i.v. administration, compared to the saline control group which had a mean (+/- SEM) serum GH peak of 3.8 +/- 0.7 ng/ml, MK-0677 at 0.25 mg/kg significantly increased (P < 0.05) peak GH concentrations 20.4-fold (77.4 +/- 13.7 ng/ml) [16].
• A single oral 1 mg/kg dose in three dogs induced a mean GH peak of 27.6 +/- 1.5 ng/ml at 120 min, and GH levels remained elevated up to 360 min after treatment [16].
• PRL, GH, or PL in the perfusion medium [21].
• WT in nonischemic regions, however, was enhanced in the GHRP-6 group compared with the GH and vehicle groups, e.g., increase of WT after 1 h of reperfusion was greater (p <0.05) in the GHRP-6 (+53 +/- 8%) than in the GH (+14 +/- 12%) or (+14 +/- 6%) [4].

References