Effect and mechanism of ketoconazole on prolactin, GH, ACTH, LH e FSH release by tumoral rat/mouse anterior pituitary cells in vitro

• Grant number: 11/10582-1
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2011 - August 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcello Delano Bronstein
• Grantee: Marcello Delano Bronstein
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Ketoconazole, antifungal agent, which revealed a potent inhibitor of adrenal steroidogenesis, can be used in the management of Cushing's disease when it is not controlled by surgical procedure and/or radiotherapy. Although it was expected that, with the reduction of serum cortisol levels and urinary occurrance elevation of plasma ACTH, this fact is often not observed. A hypothesis to explain this finding would be additional share of ketoconazole on the tumor pituitary adrenocorticotropic.In fact, some studies in the 1980s suggested action of ketoconazole in anterior pituitary cells . Our study aims to approach this topic, evaluating the effect of ketoconazole in the hormone secretion in vitro of lineages of pituitary tumor 's secreting hormones (prolactin, GH, FSH, LH, ACTH), as well as to evaluate the expression of genes involved in apoptosis and replication of DNA by the PCR technique in real time, before and after the incubation of the ketoconazole in culture medium. (AU)