Progesterone-controlled growth hormone overproduction and naturally occurring canine diabetes and acromegaly

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Abstract
Female pet dogs exhibiting either glucose intolerance alone or glucose intolerance and acromegaly were investigated. Some dogs developed the disorder(s) during diestrus and some animals developed the disorder(s) after they were given medroxyprogesterone acetate (MPA). Elevated fasting plasma glucose levels (12.3 .+-. 1.9 mM, mean .+-. SEM [standard error of the mean]) were accompanied by fasting hyperinsulinemia (144 .+-. 21 .mu.U/ml, mean .+-. SEM) and drastic elevation of plasma growth hormone (GH) levels (112.6 .+-. 45 ng/ml, mean .+-. SEM). An i.v. glucose tolerance test (IVGTT) performed on all dogs revealed non-suppressibility of GH levels and glucose intolerance. Plasma concentrations of glucose, insulin and GH during IVGTT in affected dogs differed significantly from the concentrations measured in normal dogs during the same test. MPA withdrawal and/or ovariohysterectomy (OVx-HYx) in affected animals was followed by reversal of GH levels to normal and improved glucose tolerance. Acromegaly associated soft tissue changes were also reversible after MPA withdrawal and/or OVx-HYx when GH levels had dropped. In 5 dogs which had developed diabetes during diestrus and in which a spontaneous decrease in plasma progesterone occurred during the investigation a concomitant decrease in GH levels was observed. Plasma GH measured at different stages of pregnancy in 45 dogs was found to be elevated in one animal only. The development of spontaneous diabetes/acromegaly occurring in some female dogs is related to progestagen (progesterone/MPA) exposure and that reversal of the signs is achieved by progesterone/MPA withdrawal. Apparently, diabetes/acromegaly in the dogs studied was caused by progesterone/MPA-evoked GH elevation. Apparently, the GH axis normally not appreciably responsive to progestagen exposure in some dogs becomes and/or is paradoxically controlled by physiologic levels of endogeneous progesterone or low doses of MPA.