GH-IGF1-Insulin Axis in the Prepubertal Testis: Possible Relation to Gonadotropin-Independent Steroidogenesis
Presentation Number: SUN 256
Date of Presentation: April 2nd, 2017
Paula Aliberti*, Maria Sonia Baquedano, Nora Isabel Saraco, Roxana Marino, Marco A. Rivarola, Esperanza Beatriz Berensztein and Alicia Belgorosky
Hospital de Pediatria Garrahan, Argentina
In normal boys, insulin resistance, serum IGF1 (1) and bio-available serum testosterone levels (2) increase in late prepuberty and puberty, while this physiological changes, as well as puberty onset, are delayed in GH deficiency and GH resistance patients (3) inciting the question if local changes of the GH-IGF1-insulin axis could have a role in the interstitium maturation previous to puberty.
The objective was to evaluate throughout pre-puberty the expression of genes involved in the GH-IGF1 and insulin pathways and the possible relationship with the front and backdoor steroidogenic pathways.
Prepubertal testes, confirmed by histology analysis, were collected at time of necropsy from 18 subjects without endocrine or metabolic diseases. Samples were divided in two groups: 1) Infancy, which includes minipuberty, n=8 (median age 1.3 month, range 2 days-7 months), and 2) Childhood, n=10 (median age 6 years, range 1-9 years). The gene expression of the GH-IGF1-insulin axis (GHR, IGF1, IGF1R, INSR) and the front (CYP17A1, HSD3B2) and backdoor steroidogenic pathway (SRD5A1, SRD5A2, AKR1C1, AKR1C3, AKR1C4) was assessed by RTqPCR.
Except for SRD5A2 and AKR1C4, not detected in any sample, all the other analyzed genes were expressed in every tissue. The expression of CYP17A1 mRNA was significantly higher in Infancy than in Childhood (p< 0.01), while IGF1R, SRD5A1 and AKR1C3 were significantly higher in Childhood (p<0.05). Multiple correlation studies revealed in Infancy a strong negative correlation between IGF1 and CYP17A1 expression (r=-0.95, p=0.0003) as well as a positive correlation between the backdoor enzymes AKR1C1 and AKR1C3 (r= 0.79, p=0.02). In Childhood, a positive lineal correlation with age was found for CYP17A1 (p=0.03, r=0.7) and AKR1C3 (p=0.03, r=0.7) expression. Also, a positive correlation was observed between IGF1R and CYP17A1(r=0.65, p=0.04) as well as between the backdoor enzymes AKR1C3 and SRD5A1 (r=0.69, p=0.03), and AKR1C3 and AKR1C1 (r=0.76, p=0.01). A negative correlation was found between the receptors IGF1R and INSR (r= -0.72, p=0.02), as well as between INSR and CYP17A1 (r=-0.78, p=0.01), and INSR and AKR1C3 (r=-0.63, p=0.05).
To our knowledge, we are the first to describe the backdoor steroidogenic enzymes mRNA expression throughout the entire prepubertal period, showing a higher expression in Childhood. We report an increase with age of the back and front door enzymes expression in Childhood, period independent of gonadotropins. The correlations observed at both developmental stages between the GH-IGF-I axis and the enzymes could point to a possible local role of the axis in the maturation of the prepubertal testicular interstitium. Moreover, we propose that peripheral metabolic signals, like the increase in insulin resistance and IGF1 serum levels observed in normal late prepubertal boys, could be involved in the interstitium maturation observed at this stage.
Nothing to Disclose: PA, MSB, NIS, RM, MAR, EBB, AB