In the dog endogenous progesterone and synthetic progestins may incite
overproduction of GH, resulting in acromegaly and insulin resistance.
This progrestin-induced excessive GH secretion is characterized by di
sappearance of the pulsatile secretion pattern and insensitivity to bo
th stimulation with GHRH and inhibition with a somatostatin analog. Th
is progestin-induced GH hypersecretion is not associated with neoplast
ic transformation at the pituitary level. These observations were the
impetus for a search of a possible extrapituitary site of GH productio
n. In four ovariohysterectomized dogs elevated plasma GH levels (46.5
+/- 7.7 mu g/liter; mean +/- SEM) were induced by administration of sy
nthetic progestins. In these dogs hypophysectomy did not led to a sign
ificant decrease in plasma GH levels. Analysis of the GH content of va
rious tissue homogenates revealed that the highest GH immunoreactivity
was found in extracts of the mammary gland. Ectopic production of GH
in the mammary gland was confirmed by lowering of plasma GH concentrat
ion to values within the reference range within 2 h after complete mam
mectomy in two dogs with progestin-induced elevations of plasma GH lev
els. In one of these dogs the arterial and venous GH concentrations ac
ross the mammary gland were measured and an arterio-venous GH gradient
was demonstrated. Displacement studies in the RIA and analysis by rev
ersed-phase HPLC revealed that mammary-derived GH is highly similar to
pituitary-derived GH. Immuno-histochemical staining revealed that GH
immunoreactivity was localized in focal areas of hyperplastic ductular
epithelium. In mammary tissue of healthy untreated female dogs no GH
immunoreactivity was found. It is concluded that treatment of dogs wit
h synthetic progestins can induce the overproduction of GH in the mamm
ary grand. This GH is biologically active, highly similar to pituitary
derived GH, and originates from foci of hyperplastic ductular epithel
ium of the mammary gland.