Effect of mitotane on pituitary corticotrophs in clinically normal dogs.
OBJECTIVE
To evaluate the effects of mitotane administration on the function and morphology of pituitary corticotrophs in clinically normal dogs.


METHODS
12 clinically normal adult Beagles.


METHODS
Dogs were randomly assigned to the control group or the mitotane treatment group. In mitotane treatment group dogs, mitotane was administered for 1 month. In both groups, ACTH stimulation testing and corticotrophin-releasing hormone (CRH) stimulation testing were performed. Magnetic resonance imaging (MRI) of the pituitary gland and brain was performed in mitotane treatment group dogs before and after administration of mitotane. After CRH stimulation testing and MRI, dogs were euthanatized and the pituitary gland and adrenal glands were excised for gross and histologic examination.


RESULTS
ACTH concentrations in mitotane treatment group dogs were significantly higher than in the control group dogs following CRH stimulation. Magnetic resonance imaging revealed that pituitary glands were significantly larger in treatment group dogs after administration of mitotane, compared with before administration. On gross and histologic examinations, the adrenal cortex was markedly atrophied. Immunohistochemistry revealed hypertrophy of corticotrophs in pituitary glands of mitotane treatment group dogs.


CONCLUSIONS
These findings indicate that inhibition of the adrenal cortex by continuous administration of mitotane leads to functional amplification and morphologic enhancement of corticotrophs in clinically normal dogs. In instances of corticotroph adenoma, hypertrophy of individual corticotrophs induced by mitotane may greatly facilitate enlargement of the pituitary gland and increases in ACTH secretion.
Taoda
Takahiro
T
Department of Veterinary Science, Division of Veterinary Surgery, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musasino-shi, Tokyo 180-8602, Japan.
Hara
Yasushi
Y
Takekoshi
Susumu
S
Itoh
Johbu
J
Teramoto
Akira
A
Osamura
Robert Y
RY
Tagawa
Masahiro
M
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006262:Health; D008297:Male; D008939:Mitotane / Q000494:pharmacology*; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone