Characterization and regulation of somatomedin‐C/insulin‐like growth factor I (Sm‐C/IGF‐I) receptors on cultured pig Leydig cells

Abstract

We have characterized somatomedin‐C/insulin‐like growth factor I (Sm‐C/IGF‐I) receptors in cultured pig Leydig cells by binding and cross‐linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell were 1.8 ± 0.2 × 10−9 M and 12200 ± 3200 respectively. Under reducing conditions, disuccinimidyl suberate cross‐linked 125I‐Sm‐C to one receptor complex with apparent Mr= 120000. Continuous treatment of Leydig cells with increasing concentrations of human chorionic gonadotropin (hCG) for 48 h resulted in a dose‐dependent (ED50 0.05 nM) increment in IGF type I receptors (2.5–3‐fold increase). Conversely, treatment of Leydig cells for 48 h with increasing concentrations of Sm‐C/IGF‐I produced a 3–4‐fold increase in hCG receptors. This effect was dose‐dependent (ED50= 7 ng/ml). Sm‐C/IGF‐I treatment also enhanced Leydig cell responsiveness to hCG for both cAMP (6‐fold) and testosterone (8‐fold). Moreover the stimulatory effects of Sm‐C/IGF‐I on cells cultured either in the absence or presence of 5% human serum from an hypopituitary patient were inhibited by anti‐(Sm‐C/IGF‐I) antibodies. Taken together these results not only show that Leydig cells must be considered as targets for Sm‐C/IGF‐I, but also lend support to the possibility that Sm‐C/IGF‐I plays a role in the regulation of Leydig cell function. Moreover, they suggest that Sm‐C/IGF‐I might be responsible for the delayed puberty observed in some patients with isolated growth hormone deficiency.

Effects of Growth Hormone and Insulin-Like Growth Factor I on Testosterone Secretion in Premature Male Rats.

“…It has been shown that cultured rat Sertoli cells produced IGF-I [12], and cultured pig Leydig cells contain specific IGF-I receptor, and IGF-I enhances not only LH receptor, but also the coupling of the receptor to adenylate cyclase [13,14]. No direct effects of GH on testosterone production in isolated Leydig cells have been observed in our study.…”

Growth Hormone Advances Spermatogenesis in Premature Rats Treated with Gonadotropin-Releasing Hormone Agonist.

“…Concerning the mechanism of GH action, the relevance of IGF-I to testicular function is suggested by many observations indicating that both Leydig and Sertoli cells produce and contain specific IGF-I receptors [25][26][27][28][29] and that IGF-I increases LH receptor and steroidogenic response to hCG in GH-deficient mice [30]. These findings would suggest that GH directly or GH mediated by IGF-I is involved with testicular testosterone action.…”

Régulation paracrine des fonctions leydigiennes

“…I'IGF-I. L'IGF-I augmente ie nombre de r6cepteurs ~t LH/hCG, la production d'AMPc et de testost6rone par la ceilule de Leydig, en r6ponse ~t une stimulation par hCG [5,20]. Les cellules de Sertoli s6cr~tent un peptide qui ales m~mes propri6-t6s physicochimiques et biologiques que I'IGF-I purifi6 humain et I'IGF-I obtenu par g6nie g6n6tique.…”