Cellular basis of prolactin action: involvement of cyclic nucleotides, polyamines, prostaglandins, steroids, thyroid hormones, Na/K ATPases and calcium: relevance to breast cancer and the menstrual cycle.
The mechanisms of prolactin action are uncertain. Prolactin effects are characterised by great variability in the prolactin concentration required to produce a response and by the frequent occurrence of "bell-shaped" dose response curves. Relationships between prolactin and thyroid hormones and steroids are difficult to understand: both steroids and thyroid hormones may potentiate or inhibit prolactin effects in different situations. At the second messenger level, claims have been made that cyclic nucleotides, polyamines, Na/K ATPases and prostaglandins are involved. There is evidence that prostaglandin E1 may be an important second messenger and it is proposed that this is the clue to understanding the complexity. At low concentrations PGE1 enhances intracellular calcium release and at high concentrations PGE1 inhibits calcium release. The other second messengers proposed are all probably dependent upon calcium. Many prolactin effects may involve both PGE1 and another second messenger: at low prolactin concentrations PGE1 will potentiate the other messenger whereas at high concentrations the PGE1 effect will be inhibitory leading to a bell-shaped response. Thryoid hormones seem to enhance while glucocorticoids inhibit PGE1 synthesis. PGE1 dependent effects will thus be enhanced by thyroid hormone and blocked by cortisol. The reverse will be true of effects dependent on other second messengers.
D001943:Breast Neoplasms / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology; D007328:Insulin / Q000502:physiology; D008598:Menstruation; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D011388:Prolactin / Q000502:physiology*; D011458:Prostaglandins E / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013963:Thyroid Hormones / Q000502:physiology
D007328:Insulin; D011458:Prostaglandins E; D013963:Thyroid Hormones; D011374:Progesterone; D011388:Prolactin; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D006854:Hydrocortisone