A novel targeted therapy of Leydig and granulosa cell tumors through the luteinizing hormone receptor using a hecate-chorionic gonadotropin beta conjugate in transgenic mice.

We investigated the antitumoral efficacy, endocrine consequences, and molecular mechanisms underlying cell death induced by the Hecate-chorionic gonadotropin (CG)beta conjugate, a fusion protein of a 23-amino acid lytic peptide Hecate with a 15-amino acid (81-95) fragment of the human CGbeta chain. Transgenic (TG) mice expressing the inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T-antigen (Tag) transgene, developing luteinizing hormone (LH) receptor (R) expressing Leydig and granulosa cell tumors, and wild-type control littermates were treated either with vehicle, Hecate, or Hecate-CGbeta conjugate for 3 weeks. Hecate-CGbeta conjugate treatment reduced the testicular and ovarian tumor burden (P < .

Adrenocortical tumorigenesis in transgenic mice expressing the inhibin alpha-subunit promoter/simian virus 40 T-antigen transgene: relationship between ectopic expression of luteinizing hormone receptor and transcription factor GATA-4.

We have analyzed the ontogeny and putative mechanisms of transregulation of LH receptor (LHR) and transcription factor GATA-4, coexpressed during the adrenocortical tumorigenesis of prepubertally gonadectomized transgenic (TG) mice expressing the inhibin alpha-subunit promoter/simian virus 40 T-antigen (inhalpha/Tag) transgene. The onset of adrenal LHR mRNA and protein expression coincided with that of GATA-4 at the age of 4 months and preceded the appearance of discernible adrenal tumors at about 6 months. In situ hybridization and double-immunohistochemistry demonstrated colocalization of the LHR and GATA-4 messages and proteins in the adrenal cortex.