Mutant Prolactin Receptor and Familial Hyperprolactinemia

compare the mutant prolactin receptor with other mutant endocrine receptors (parathyroid hormone and growth hormone) characterized by loss of function (hypocalcemia and short stature, respectively).The authors attempt to explain the reproductive abnormalities in their pedigree as being the result of hyperprolactinemia and excessive signaling by the prolactin receptor.They point out the persistent postpartum galactorrhea of the proband is indicative of excess prolactin signaling.However, they report a loss of function in relation to this mutation in heterologous systems.Hyperprolactinemia in the presence of a loss-of-function mutation would not lead to increased signaling.One possibility is that the reproductive abnormalities are mediated by a second receptor, as is the case in syndromes of resistance to other hormones (thyroid hormone and glucocorticoids).Alternatively, the reproductive abnormalities seen could be due to loss of function.One way to resolve this question would be to determine the patients' clinical response to cabergoline: if oligomenorrhea and infertility were due to excess prolactin signaling, one would expect these conditions to resolve with the normalization of prolactin levels after treatment with a dopamine agonist, and if these condition were due to a loss of function in prolactin-receptor signaling, then dopamine agonist treatment would have no effect, despite the normalization of prolactin levels.