Alleviation of estrogen-induced hyperprolactinemia through intracerebral transplantation of hypothalamic tissue containing dopaminergic neurons.
Prolactin-secreting pituitary tumors can be induced in young rats through prolonged estrogen treatment. Recent evidence suggests that such tumors are associated with a degeneration of tuberoinfundibular dopaminergic (TI-DA) neurons, which normally inhibit prolactin secretion by the anterior pituitary's lactrophs. For this study, chronic hyperprolactinemia was induced in young, ovariectomized Fisher 344 rats through Silastic capsule implants of 17 beta-estradiol, placed subcutaneously for 1 month prior to removal. Rats with such estrogen-induced hyperprolactinemia then received transplants of neonatal arcuate-median eminence (ME) tissue (containing TI-DA neurons) or amygdala (control) tissue, placed either within the third ventricle or bilaterally within the hypothalamus. Blood samples were obtained 1 month after transplantation and prolactin concentrations measured by radioimmunoassay. Two of 4 animals receiving ventricularly-placed arcuate-ME transplants and 4 of 7 animals receiving bilateral arcuate-ME transplants showed substantial reductions in plasma prolactin levels compared to mean values in control animals. Follow-up catecholamine (CA) histochemistry indicated a bright fluorescence intensity in the median eminence of animals remaining hyperprolactinemic with ineffective transplants. Furthermore, in sharp contrast to the very low, nonpulsatile LH levels found during a second bleeding in recipients bearing ineffective transplants, recipients with effective arcuate-ME transplants had the high, pulsatile levels of LH characteristic of normal, ovariectomized rats. These data suggest that developing TI-DA neurons, within effective arcuate-ME transplants, became functional to reinstate or accentuate DA inhibition of prolactin secretion and, in so doing, indirectly normalized LH secretion as well.
D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000637:transplantation; D001921:Brain / Q000502:physiology*; D002552:Cerebral Ventricles / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006966:Hyperprolactinemia / Q000503:physiopathology*; D007031:Hypothalamus / Q000637:transplantation*; D007033:Hypothalamus, Middle / Q000503:physiopathology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008473:Median Eminence / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation; D009474:Neurons / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D012826:Silicone Elastomers
D012826:Silicone Elastomers; D004958:Estradiol; D007986:Luteinizing Hormone; D004298:Dopamine