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

BOJORGE, MARIANA; CICCONI, NADIA SOFÍA; MIQUET, JOHANNA GABRIELA; ANA ISABEL SOTELO; DÍAZ MARÍA EUGENIA

Mar del Plata

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

Sociedad Argentina de Investigación Clínica

Recombinantgrowth hormone (GH) is used for the treatment of different pathologies, includingpediatric and adult GH deficiency, chronic renal insufiency, Turner syndromeand cachexia secondary to AIDS.The main disadvantages of GH administration are the short half-life of thehormone, its renal toxicity and the necessity of multiple injections whichturns the treatment stressing and uncomfortable for the patients; thus GH is agood candidate for depot formulation producing continuous release of GH. However,the effects of different modes of GH administration over cell proliferation andtumorigenesis are not known. Considering that high GH levels have beenassociated with the development of tumors in humans and given that transgenicmice overexpressing GH show increased tendency to develop cancer, the purposeof the present work is to study the differential effects of both GHadministration patterns, intermittent and continuous, on the expression ofreceptors involved in mammary tissue growth and development, and the inductionof signaling pathways involved in cell proliferation and survival. For thispurpose, female mice were implanted with osmotic pumps for sustain release ofGH or they were administrated GH by intermittent injections. The effects ofdifferent GH administration patterns over the expression of ERa,EGFR and IGF-1R were assessed by Western Blot. Besides several early genesprotein like c-fos, c-myc and c-jun as well the protein content and basalactivation of Akt and Scr was assessed, too.Resultsshowed that intermittent injections of GH induced an up-regulation of EGFR,IGF-IR and c-fos protein content as well as an increased in Akt basalactivation. However, continuous GH delivery didn´t have any significantmolecular effects in breast tissue. Accordingto previous findings from the research group described in mice liver tissue, itcould be suggested that sustained GH delivery would have less promitogenicconsequences in breast tissue.