Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance)

Abstract

Serum gonadotrophins, androgens, insulin and insulin-like growth factor-I (IGF-I) were determined before and during long-term treatment with recombinant IGF-I of seven males with Laron syndrome, and the changes correlated with changes in testicular volume and penile size. The subjects were four boys below the age of 5, two boys aged 10 and 14 but prepubertal and one 28-year-old fully sexually developed adult. IGF-I was administered by a once daily subcutaneous injection of 150 mg/kg per day to the boys and 120 mg/kg per day to the adult patient.In the very young boys no change in serum gonadotrophins, androgens, gonads or genitals was registered. In the two older boys and the adult patient, there was a progressive rise in luteinizing hormone, follicle-stimulating hormone and testosterone. Concomitantly, there was an increase in size of the testes and penile length. The two boys started puberty. As very high serum IGF-I levels were registered in the adult patient, the daily dose was progressively decreased to 70 mg/kg per day. Stopping the IGF-I administration in this patient, according to the protocol, led to a return to pretreatment serum levels and testicular and penile size.This report shows for the first time a direct effect of IGF-I on sex hormones and sex organs in the male.

Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men

“…In analogy, patients with Laron dwarfism have delayed and prolonged puberty, and in some cases IGF1 treatment has led to a marked increase in levels of androgens (3). In accordance with the biochemical observations, decreased penile size at birth and cryptorchidism have been observed in patients with isolated GH deficiency/GH insensitivity, supporting that GH action is important for full masculinization (3,5,6,7,8).…”

“…The influence of GH/IGF1 activity seems to involve reproductive hormone levels (2, 3), semen characteristics (2,4) and phenotype (e.g. penile size and risk of cryptorchidism) (3,5,6,7,8). The clinical observations are supported by histological studies identifying GH and IGF1 receptors in Leydig, Sertoli, and germ cells as well as in the accessory reproductive glands (1,9,10).…”

Identification of the growth hormone receptor in an advanced teleost, the tilapia (Oreochromis mossambicus) with special reference to its distinct expression pattern in the ovary

“…Coadministration of GH with gonadotropin (GTH) has also been used to induce ovulation in patients who show poor sensitivity to GTH (Homburg 1996). Furthermore, Laron syndrome, GH insensitivity resulting from a variety of GH receptor (GH-R) mutations, shows a hereditary dwarfism, truncal obesity, and delayed puberty, which are restored by IGF-I treatment (Laron & Klinger 1998).…”

A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings

“…The adult male patient with STAT5B mutation previously described had normal LH, FSH, and testosterone despite elevation of PRL levels (7,8), suggesting a lack of action of circulating PRL. The pubertal delay observed in patients with STAT5B defects can be explained by the state of chronic illness or related to the low levels of circulating IGF1 (20)(21)(22). For this reason, at this moment, we did not recommend any specific treatment for the mild hyperprolactinemia observed in these patients.…”