Role of Gonadotropin in the Control of IGF1R Expression By Interstitial Cells in Human and Monkey Testis throughout Postnatal Development: Implications for Leydig Cell Differentiation

Presentation Number: THR-117
Date of Presentation: March 5th, 2015

Paula Aliberti*1, Suresh Ramaswamy2, Tony M. Plant2, Roberto Ponzio3, Diego Chirico1, Marco A. Rivarola4, Alicia Belgorosky5 and Esperanza Beatriz Berensztein1
1Garrahan Pediatric Hospital, Buenos Aires, Argentina, 2University of Pittsburgh School of Medicine and Magee Womens Research Institute, Pittsburgh, PA, 3School of Medicine, University of Buenos Aires, Buenos Aires, Argentina, 4Hospital de Pediatria Garrahan, Argentina, 5Hospital de Pediatría Garrahan, Buenos Aires, Argentina

Abstract

There is evidence that the growth hormone (GH)-insulin like growth factor (IGF) axis is involved in regulating Leydig cell differentiation, and in modulating androgen steroidogenesis (1). IGF-1 is a critical factor in the control of adult Leydig cell number and maturation (2). In addition, IGF-2 is able to regulate steroidogenesis in rat Leydig cells (3). We have previously proposed that IGF-2, mainly through the insulin receptor (IR), is also involved in Leydig cell differentiation in prepubertal human testes (4). In vivo stimulation with either LH or FSH+LH in early juvenile monkeys induced testosterone secretion (5).

Aim of this study: 1) to compare the immunoexpression of IGF1R by interstitial cells in testis from human (HT) and rhesus monkey (Macaca mulatta)(MT)from birth to adulthood, and 2) to examine the effect of precocious in vivo stimulation with FSH and LH (either alone or in combination) on immunoexpression of this receptor in the testicular interstitium of juvenile monkeys.

Clinical Material and Methods: Chemicon Mab1120 specific anti-IGF1R antibody was used for immunohistochemistry. HT (n=18) were collected at the time of necropsy from subjects without endocrine or metabolic diseases. Samples were grouped according to age: neonatal (< 1 month [mo], n=3), infantile (1-8 mo, n=4), juvenile (1year [y] to puberty, n=4), pubertal (13 -15 y, n=7). MT (n=17) were obtained at the time of castration: neonatal (1-2 day [d] , n=3), infantile (4-5 mo, n=3), juvenile (14-36 mo, n=6), pubertal (38-51 mo, n=2) and adult (60 mo, n=3). To evaluate the effect of in vivo gonadotropin stimulation on IGFR immunoexpression by prepubertal interstitial cells, juvenile monkeys received 11-day treatments (n=3) with vehicle, FSH, LH or LH+FSH (5).

Results: In both species, all cells exhibiting the characteristic histological appearance of Leydig cells (LC) were positive for IGF1R expression in neonatal, infantile, pubertal and adult testes; positive cells, however, were not observed in early and mid-juveniles: stages of development devoid of morphologically identified LC. In juvenile monkeys in vivo LH or FSH stimulation for 11 days failed to induce immunoexpression of IGF1R in LCs, while the combined FSH+LH treatment resulted in some lightly positive LCs.

Conclusion: In HT and MT, IGF1R expression by the LC throughout postnatal development was directly correlated with stages of elevated gonadotropin and testosterone secretion. IGF1R expression may therefore be considered as a marker of LCs. However, precocious LH and FSH stimulation of the juvenile MT resulted in an adult pattern of testosterone secretion but did not induce full pubertal IGF1R expression. These findings indicate that in primates IGF1R is not involved in LCs functional differentiation, reinforcing the hypothesis that IGF-1/IGF-2 might act through IR, which is highly expressed in immature HT(4).

 

Nothing to Disclose: PA, SR, TMP, RP, DC, MAR, AB, EBB