scholarly journals Increased Testicular Insulin-like Growth Factor 1 is Associated with Gonadal Activation by Recombinant Growth Hormone in Immature Rats

2021 ◽  
Author(s):  
Yang Xu ◽  
Chang Yong Han ◽  
Mi Jung Park ◽  
Myung Chan Gye
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Leydig Cells ◽  
Daily Injection ◽  
Marker Genes ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Recombinant Growth Hormone ◽  
Testosterone Levels ◽  
Immature Rats

Abstract To understand the mechanism of precocious sexual maturation following prepubertal growth hormone (GH) therapy, the effects of recombinant human GH (rhGH) on the kisspeptin-gonadotropin-releasing hormone-luteinizing hormone (GnRH-LH) system in the hypothalamus-pituitary axis, systemic and testicular insulin-like growth factor-1 (IGF1), spermatogenesis and Leydig cell steroidogenesis, and circulating testosterone levels were examined in immature rats. Following daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30, testicular steroidogenic pathway genes and spermatogenesis marker genes mRNA levels, the number and size of HSD17B(+) Leydig cells, and blood testosterone levels in the rhGH rats were significantly higher than those of controls on PNDs 24 and 31. Hypothalamic Kiss1 and Gnrh1 mRNA in the rhGH rats were significantly higher than those in the controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. Hypothalamic Igf1 mRNA levels in rhGH rats were significantly higher than those in the controls on PND 24 but significantly lower than those in controls on PND 31. Testicular Igf1 mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas liver Igf1 mRNA levels and circulating IGF1 levels were not. In progenitor Leydig cells, rhGH significantly increased the Igf1 and steroidogenic pathway genes mRNA levels and the testosterone production. Therefore, local increases in testicular IGF1 might be an important mediator of gonadal activation via steroidogenic activation of Leydig cells in immature rats given rhGH.

scholarly journals Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

2000 ◽  
Vol 167 (2) ◽  
pp. 295-303 ◽  
Author(s):  
JW van Neck ◽  
NF Dits ◽  
V Cingel ◽  
IA Hoppenbrouwers ◽  
SL Drop ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Receptor Antagonist ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Gh Receptor ◽  
Igf I ◽  
Igfbp 3

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1.25, 2.5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2.5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups. In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.

Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo

1994 ◽  
Vol 131 (4) ◽  
pp. 405-412 ◽  
Author(s):  
Bronwyn A Crawford ◽  
David J Handelsman
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Recombinant Growth Hormone ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Human Primate ◽  
Stimulation Of

Crawford BA, Handelsman DJ. Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo. Eur J Endocrinol 1994;131:405–12. ISSN 0804–4643 In vitro studies indicate a physiological role for insulin-like growth factor I (IGF-I) in paracrine regulation of testicular function and recent clinical studies suggest a potential role for growth hormone (GH) and/or IGF-I in the treatment of hypogonadotrophic states in males. This study aimed to examine the effects of pretreatment with recombinant human GH (rhGH) or rhIGF-I on the response to gonadotrophins of the non-human primate testis in vivo. Using a balanced Latin square design with repeated measures, six prepubertal male hamadryas baboons (Papio hamadryas hamadryas) were treated in a cross-over sequence for periods of 18 days with daily im injections of rhGH (0.4 IU·kg−1 · day−1), rhIGF-I (0.1 mg·kg−1 · day−1) or saline with a 2-week washout period between each treatment. A single im injection of hCG (1500 IU) increased serum testosterone (p = 0.0002) but neither rhGH nor rhIGF-I influenced the timing or magnitude of this response (p > 0.5). A single im dose of FSH (75 IU) stimulated immunoreactive inhibin (p = 0.01) but also was unaffected in magnitude or timing by pretreatment with rhGH or rhIGF-I (p> 0.2). Circulating IGF-I levels were increased independently by hCG (p = 0.01) and FSH (p < 0.0001) administration. These findings indicate that neither GH nor IGF-I pre-treatment enhance acute gonadal responses to gonadotrophin stimulation of the prepubertal non-human primate testis in vivo. These findings suggest that GH or IGF-I treatment of hypogonadotrophic men without somatotrophin deficiency is unlikely to be beneficial. David J Handelsman, Andrology Unit, Royal Prince Alfred Hospital, Departments of Medicine and Obstetrics and Gynaecology, University of Sydney, Sydney 2006, Australia

scholarly journals Administration of bovine, porcine and equine growth hormone to the horse: effect on insulin-like growth factor-I and selected IGF binding proteins

2001 ◽  
Vol 171 (1) ◽  
pp. 163-171 ◽  
Author(s):  
SS De Kock ◽  
JP Rodgers ◽  
BC Swanepoel ◽  
AJ Guthrie
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Protein Markers ◽  
Recombinant Growth Hormone ◽  
Igf Binding Proteins ◽  
Thoroughbred Horses ◽  
Igf I ◽  
Igf Binding ◽  
Time Required

This study investigated the biochemical effects of administration of three types of recombinant growth hormone (GH; somatotropin) to the Thoroughbred horse. Equine or bovine or porcine GH was administered at a recommended dosage to 3-5-year old Thoroughbred geldings, for up to 21 days. It was shown that, in addition to equine GH, bovine and porcine GH were active in the horse; however, porcine GH caused injection-site reactions that were so serious that administration had to be terminated. The concentrations of a range of GH-related serum protein markers were determined before, during and after the administration period. Because of the short half-life of GH itself, the objective was to identify GH-related markers that showed changes in concentration and which could be used as indicators of the abuse of these hormones. Among the possible markers identified, serum total insulin-like growth factor (IGF)-I was shown to be the most promising, increasing to 270% of the basal concentration for equine GH administration. After GH administration, IGF-I took longer to attain baseline concentrations than the time required for GH concentrations to recover to normal. The concentration obtained from the administration significantly exceeded natural concentrations for IGF-I, as was determined from a population of more than 2000 Thoroughbred horses in three continents. The concentrations of serum free IGF-I and IGF binding protein 3 (IGFBP-3) were also shown to be significantly affected by equine and bovine GH.

scholarly journals Fetal rat lung epithelium has a functional growth hormone receptor coupled to tyrosine kinase activity and insulin-like growth factor binding protein-2 production

1998 ◽  
Vol 21 (1) ◽  
pp. 73-84 ◽  
Author(s):  
DC Batchelor ◽  
RM Lewis ◽  
BH Breier ◽  
PD Gluckman ◽  
SJ Skinner
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Binding Protein ◽  
Fetal Lung ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Rat Lung ◽  
Lung Epithelium ◽  
Fetal Rat ◽  
Fetal Rat Lung

Although growth hormone (GH) receptor (GHR) mRNA and protein are present in fetal tissues such as the lung, there is little evidence that GH mediates growth in the fetus. We have identified functional responses to GH in fetal rat lung epithelia and suggest a possible role for GHR in the developing lung. GHR mRNA in lung extracts was high before birth at day 16 of gestation (16f), decreased to low levels at day 22f but increased again after birth. At day 20f GHR mRNA levels were higher in lung than in liver, whereas growth hormone binding protein mRNA levels were approximately equal in lung and liver. Stimulation of primary cell cultures of day 19f lung epithelia with GH caused increased tyrosine phosphorylation in specific proteins, demonstrating functional GHR. Lung fibroblasts isolated at the same time did not respond to GH. Ligand and Northern blot analysis of the epithelial cultures revealed that GH stimulation increased insulin-like growth factor binding protein-2 (IGFBP-2) activity and mRNA. These experiments demonstrate the functional activity of GHR, specifically in fetal lung epithelium. We suggest that one role for GH in vivo may be indirectly to modify insulin-like growth factor activity in the developing fetal lung by increasing IGFBP-2.

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