Inhibitory effects of mitotane on viability and secretory activity in mouse gonadotroph cell lines.
Mitotane represents the mainstay medical treatment for metastatic, inoperable or recurrent adrenocortical carcinoma. Besides the well-known adverse events, mitotane therapy is associated also with endocrinological effects, including sexual and reproductive dysfunction. The majority of male patients undergoing adjuvant mitotane therapy show a picture of hypogonadism, characterized by low free testosterone and high sex hormone binding globulin levels and unmodified LH concentrations. Since mitotane has been shown to have direct pituitary effects, we investigated whether mitotane may influence both cell viability and function of gonadotroph cells in the settings of two pituitary cell lines. We found that mitotane reduces cell viability, induces apoptosis, modifies cell cycle phase distribution and secretion of gonadotroph cells. The present data strengthen previous evidence showing a direct mitotane effect at pituitary level and represent a possible explanation of the lack of LH increase following decrease in free testosterone in patients undergoing adjuvant mitotane therapy.
Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Italy; Laboratorio in Rete del Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of Ferrara, Italy.
Erica
E
Gentilin
Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Italy.
Daniela
D
Molè
Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Italy.
Teresa
T
Gagliano
Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Italy.
Mariella
M
Minoia
Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Italy.
Maria Rosaria
MR
Ambrosio
Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Italy; Laboratorio in Rete del Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of Ferrara, Italy.
Ettore C
EC
Degli Uberti
Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Italy; Laboratorio in Rete del Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of Ferrara, Italy. Electronic address: ztlmch@unife.it.
Maria Chiara
MC
Zatelli
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D052681:Gonadotrophs / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D008939:Mitotane / Q000633:toxicity*
D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7
Adrenocortical carcinoma; FSH; Hypogonadism; LH; Mitotane; Pituitary function