Progestin treatment in the dog. I. Effects on growth hormone, insulin-like growth factor I and glucose homeostasis.
The effects of two synthetic progestins, medroxyprogesterone acetate (MPA) and proligestone (PROL), on the release of growth hormone (GH) and glucose metabolism were studied in two groups of eight ovariohysterectomized dogs. Eight injections of long-acting progestins were administered at 3-week intervals. Recovery was studied in four dogs of each treatment group in the 6 months following cessation of progestin administration. Treatment with both MPA and PROL resulted in similar increases in plasma levels of GH and insulin-like growth factor I (IGF-I). The GH responses to both clonidine and growth hormone-releasing hormone became impaired. In neither treatment group did the elevated plasma GH levels decrease after administration of the synthetic somatostatin analogue SMS 201-995. The size and shape of the pituitary gland were not changed by progestin treatment. After cessation of progestin administration, basal plasma levels of GH and IGF-I did not return to pretreatment values. The GH response to growth hormone-releasing hormone remained impaired for at least 6 months after the last progestin administration. In both treatment groups, glucose homeostasis was sustained initially by increased insulin production. Prolonged treatment with MPA and PROL resulted in glucose intolerance. No amelioration was observed during the recovery period in either group. A small number of dogs developed diabetes mellitus. In more than 50% of the dogs in both treatment groups small mammary tumours developed. The recently discovered local production of GH probably played a role in mammary tumorigenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Selman
P J
PJ
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Mol
J A
JA
Rutteman
G R
GR
Rijnberk
A
A
D000302:Adrenal Cortex / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology; D015994:Incidence; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000453:epidemiology / Q000209:etiology; D008525:Medroxyprogesterone / Q000494:pharmacology; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism / Q000502:physiology; D011374:Progesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D011372:Progestins; D011374:Progesterone; C017677:proligestone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008525:Medroxyprogesterone; D005947:Glucose