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Effects of growth hormone on neuroendocrine function

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EN
Although the role og growth hormone (GH) in the control of reproductive functions is not well understood, there is considerable evidence that the states of both GH deficiency and GH excess are typically associated with reproductive deficits.To identify the possible involvement of functinal alternations in the hypothalmic-pituitary system in producing these deficits, we are studying neuroendocrine function related to reproduction in transgenic animals overexpressing GH, in animals with congenital GH deficiency, and in animals with selective immunonoutralization of GH.The results indicate that GH acts on the hypothalmus to alter dopaminergic and noradrenergic control of prolactin and gonadotrophin release.Life-long elevation of GH levels outside the physiological range disrupts feedback control of luteininzing hormone (LH) relaese by gonadal steroids.Plasma LH and follicle-stimulating hormone (FSH) levels and feedback control of LH release are also abnormal in GH-deficient animals indicating that physiologival levels of endogenous GH are normally involved in the control of gonadotropin release.Differences between the effects of bovine vs.human GH in transgenic moce and differential effects of GH mechanisms involved in the actions of HG on the hypothalmic-pituitary system.
EN
Four transgenic pigs, produced with the use of two different gene constructs containing the bovine growth hormone coding gene - Mt-bGH-10D6 (wild type) and Mt-bGH-M8 (mutated), were used to produce the F1 generation to investigate their performance traits. No differences were observed in fattening and slaughter traits between transgenic and non-transgenic pigs. It was found that the weight of ham proper and loin eye area was significantly higher in carriers of Mt-bGH-10D6 gene constructs.
EN
Transgenic mice which overexpress growth hormone (GH) may be used a model system to examine growth, kidney pathology, as well as the medical condition known as acromegaly (hyper-growth hormone secretion). GH is a pleiotropic 22 kDa polypeptide hormone which elicits body growth in jeuvenille animals and also mediates protein, carbohydrate, and lipid metabolism. The structure / function relationships of selected residues of bovine (b) GH a-helix I were approached using site-directed mutagenesis in concert with the production of bGH analog transgenic mice. Phenyalanine (Phe, F) 11 and histidine (His, H) 22 in the amino-terminus of bGH were the targeted amino acids. bGH and the bGH analog transgenic mice all exhibited the enhanced growth phenotype similar to bGH transgenic mice and had elevated IGF-1 serum concentrations. However, bGH-H22R mice demonstrated levels of blood urea nitrogen (BUN) and serum creatinine (SCR) several fold higher than the other transgenic mice. Elevated BUN and SCR are an indication of renal insufficiency in this mouse line. Glucose tolerance testing in the bGH-H22R mice revealed that they possessed a lower tolerance for glucose, or an enhancement of the diabetogenic properties of the hormone as compared to wild-type and other GH analog transgenic mice: In addition to the glomerulosclerosis found in bGH mice, histological examination of the mature bGH-H22R mice demonstrated severe glomerulosclerosis, as well as cystic kidney lesions.
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issue 3
247-249
EN
Using fluorescence in situ hybridization (FISH) to somatic nuclear halos from transgenic rabbits WAP:6xHishGH, we present evidence for stability of transgenesis at the chromatin level. FISH performed on fibroblasts from a homozygous individual showed 2 independent loops from both chromosomes of pair 7. On a heterozygous individual, FISH detected a single loop. According to the concept of chromatin loops and their influence on gene expression, this shows that the human growth hormone transgene, which was actively expressed in mammary gland under the influence of the tissue-specific promoter, was inactive in examined skin fibroblasts.
EN
The intracerebroventricular infusions of genistein (total 40 ?g) were made in male sheep (November) to test its influence on melatonin, growth hormone (GH) and luteinizing hormone (LH) secretion. The analysis of the results encompassed 3 similar periods: before the infusion (afternoon hours), the first (evening hours), and the second (night hours) halves of the treatment. The night plasma concentration of melatonin in genistein-infused rams was significantly lower than that noted during the respective period in vehicle-infused rams. Plasma GH concentration increased significantly in both vehicle- and genistein-infused rams during the night hours, as compared with the concentrations noted during the afternoon and evening, however, genistein significantly stimulated the amplitude of GH pulses in these latter. The LH concentration was significantly lower during the second part of genistein treatment, than in vehicle-infused rams. The frequency and amplitude of LH pulses clearly tended to decrease following genistein infusion. In conclusion, genistein, acting at the central nervous system level in sexually active rams is able to reduce the secretion of melatonin and LH and has also a slight stimulatory effect on the amplitude of GH pulses.
EN
The polymorphism of kappa-casein (alleles A, B and E) and growth hormone (alleles L and V) genes was studied using PCR/RFLP method with the aim to evaluate the degree of genetic diversity of Polish Red and German Red cattle, which are endangered with extinction. At the kappa-casein locus, a very low frequency of allele B in German Red cattle was found. In both the breeds, allele E was absent. There was a relatively high frequency of allele L in the growth hormone locus, especially for German Red cattle. The results were compared with frequencies and diversities of other red cattle breeds.
EN
Growth hormone (GH) plays a central role in the regulation of growth and metabolism in animals and in humans. At the tissue levels, the pleiotropic actions of GH are mediated through their cell-surface receptor - GHR. The GHR belongs to the hematopoietic receptor superfamily. In mammals, GHR is the product of a single gene. In all studied, species GHR gene characterizes a complex structure of exon 1, coding for the 5'-untraslated region (5'-UTR). Several transcripts from the GHR gene were found differing by the presence of various length 5'-UTRs, resulting from the alternative splicing of the exon 1 fragments to a common splice site located 11-bp in the human and in bovine GHR gene exon 2. Numerous nucleotide sequence polymorphisms were found in the human GHR gene; some of them, those associated to GH resistance, were identified as the causative mutations of growth retardation, e.g. Laron's syndrome. In farm animals, genes coding for GH and GHR are obvious candidates for quantitative trait markers. Several polymorphic sites have been identified in the bovine GHR gene. At least in two cases, an association was reported between GHR gene polymorphism and performance traits. Detection of additional polymorphisms is necessary to help investigating the role of GHR variation in the production traits of the cattle. This article includes a review of literature on structure, function and polymorphism within GHR gene. Also, there are mentioned new data concerning the polymorphism recently identified by authors in the bovine GHR gene.
EN
The influence of in vivo melatonin administration on in vitro pituitary follicle stimulating hormone (FSH), growth hormone (GH) and prolactin secretion, as well as the possible influence of dopamine (DA) were evaluated in prepubertal (31-day-old), pubertal (33-day-old) and adult female rats at diestrus phase of the sexual cycle. The in vitro pituitary hormone secretions were evaluated at basal rate for the first hour of incubation only, in Krebs Ringer phosphate (KRP) (I1) and after a second hour of incubation with KRP (I2) or with KRP+DA (I2 plus DA). I1PRL secretion was significantly higher in 33-day-old control and melatonin treated (MEL) rats as compared to I2 periods. However, in 31-day-old rats I1 secretion was higher than in the I2 or I2+DA periods, in MEL rats. In vitro GH secretion was significantly higher at I1 than during I2 periods in the control 31- and 33-day-old groups, but not in MEL rats. The only significant effect of DA was the elevation of GH in prepubertal MEL rats. In vitro FSH release was increased by melatonin in 31-and 33-day-old female rats. No differences in PRL, GH and FSH secretion were found in adult rats. In conclusion, the results show that melatonin effects upon in vitro pituitary gland activity are reproductive-stage-dependent modifying the secretory capacity of the lactotrop, gonadotrop and somatotrop during prepubertal and pubertal ages but not in adult rats studied at a quiescent phase of the sexual cycle.
EN
The present study tested a hypothesis, whether plant-derived genistein influences the secretion of growth hormone (GH) in ewes, acting directly within the central nervous system (CNS). Starting six weeks after ovariectomy, ewes were infused intracerebroventricularly with genistein (n = 5) or 17beta-estradiol (n = 5), both in a total dose of 40 microg/400 microl/4 h, or with a vehicle (control, n = 5). All infusions were performed from 10:00 AM to 2:00 PM and blood samples were collected from 8:00 AM to 8:00 PM at 10-min intervals. Five genistein- and three vehicle-infused ewes were slaughtered the following morning. The plasma GH concentration was assayed by the radioimmunoassay method, and immunoreactivity of GH in the adenohypophysis was determined by immunohistochemistry. In genistein-infused ewes, mean plasma GH concentration was significantly higher during the whole period of infusion than the concomitant concentration in vehicle-infused ewes. However, examining data within group, GH secretion rose gradually, reaching a significant value during the second phase of genistein infusion. In 17beta-estradiol-infused animals, a significant increase in GH concentration was noted during the first two hours of the infusion, in comparison with vehicle-infused and also in comparison with genistein-infused ewes. Although a gradual increase in basic GH secretion continued in all treated groups during the afternoon and evening, mean plasma GH concentrations in genistein- and 17beta-estradiol-infused ewes were still significantly higher than in the vehicle-infused. The percentage of GH-positive cells in the adenohypophysis and the density of immunoreactive material in these cells decreased significantly in genistein-infused ewes, compared to the control, indicating diminished hormone storage. In conclusion, genistein as 17beta-estradiol, is an effective stimulator of GH secretion in ewes and may exert its effect at the level of the CNS.
EN
The gene construct WAP(6xHisThr):hGH containing the entire human growth hormone gene (hGH) under the rat whey acidic protein (WAP) promoter regulating the expression in mammary glands of mammals was prepared. The 5? end of the gene was modified by the addition of a sequence encoding six histidine residues and a sequence recognized by thrombin. The gene construct was introduced by microinjection into the male pronucleus of a fertilized oocyte. The founder male rabbit was obtained with the transgene mapping to chromosome 7. The presence of the growth hormone was confirmed in samples of milk collected during the lactation of F1 generation females. The growth hormone can be easily purified by affinity chromatography and cleavage by thrombin to an active form.
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