Glycoprotein hormone alpha-subunit-producing pituitary adenomas in rats treated for one year with calcitonin.
Calcitonin, a calcium-lowering hormone, has been associated with an increased incidence of nonfunctioning pituitary tumors in rats. In this study, rats were treated with calcitonin (80 IU/kg/d) for 52 weeks. After treatment with calcitonin, immunohistochemistry and in situ hybridization analyses demonstrated that most pituitary tumors expressed the glycoprotein hormone alpha-subunit. Expression of the alpha-subunit was identified rarely in hyperplastic lesions of control animals. Serum levels of GH, PRL, ACTH, LH, and FSH were unchanged in calcitonin-treated rats relative to controls. However, TSH levels were increased 2.1 fold after chronic treatment with calcitonin in both male and female rats (P less than 0.001). The level of glycoprotein hormone alpha-subunit was markedly increased (20-fold) in male rats with smaller elevations in female rats. Time course studies demonstrated that increases in serum alpha-subunit levels could be detected by 24 weeks of treatment and that elevations in alpha-subunit were present in the majority of animals by 40 weeks of treatment with calcitonin. The authors conclude that high doses of calcitonin, administered to rats for 6 months or longer, increases the incidence of alpha-subunit-producing pituitary tumors.
Thyroid Unit, Massachusetts General Hospital, Boston 02114.
J L
JL
Jameson
J
J
Weiss
J M
JM
Polak
G V
GV
Childs
S R
SR
Bloom
J H
JH
Steel
C C
CC
Capen
D E
DE
Prentice
A W
AW
Fetter
J M
JM
Langloss
D000236:Adenoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000235:genetics; D015292:Glycoprotein Hormones, alpha Subunit / Q000032:analysis / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood / Q000235:genetics; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics; D008297:Male; D009693:Nucleic Acid Hybridization; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000097:blood / Q000235:genetics; D013997:Time Factors
D015292:Glycoprotein Hormones, alpha Subunit; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D002116:Calcitonin