Growth hormone administration patterns have different molecular effects in female mice breast tissue

BOJORGE MA; CICCONI NS; MIQUET JG; SOTELO AI ; DIAZ ME ; GONZALEZ L

Mar del plata

Congreso; Reunión Conjunta SAIC, SAI, SAFIS 2018; 2018

Sociedad Argentina de Investigación Clínica

Recombinant growth hormone (GH) is used for the treatment of different pathologies, including pediatric and adult GH deficiency, chronic renal insufficiency, Turner syndrome and cachexia secondary to AIDS. The main disadvantages of GH administration are the short half-life of the hormone, its renal toxicity and the necessity of multiple injections which turns the treatment stressing and uncom-ortable for patients; thus, GH is a good candidate for depot formulations producing continuous release of the hormone. However, the effects of different GH-administration modes over cell proliferation and tumorigenesis are not known. High GH levels have been associated with the development of tumors in humans, and transgenic mice overexpressing GH show increased tendency to develop cancer. The purpose of the present work was to study the differential effects of GH administration patterns, intermittent and continuous, on the expression of receptors involved in mammary tissue growth and development, and the engagement of signaling pathways involved in cell proliferation and survival. For this purpose, female mice were implanted with osmotic pumps for sustained release of GH or they were given GH by intermittent injections. The effects of different GH administration patterns over the expression of estrogen receptor alpha (ERα), epidermal growth factor receptor (EGFR) and insulin like growth factor-1 receptor (IGF-1R) were assessed by Immunoblotting. Besides, the early genes protein c-fos, c-myc and c-jun, as well the protein content and basal activation of Akt and Src was assessed. Results showed that intermittent injections of GH induced the up-regulation of EGFR, IGF-IR and c-fos protein content as well as an increase in Akt basal activation. However, continuous GH delivery did not have any significant molecular effect in breast tissue. Current results suggest sustained GH delivery would have less promitogenic consequences in breast tissue, in accordance to previous observations in mice liver from our research group.