Prolactin-releasing activity of neurohypophysial hormones: structure-function relationship.
Oxytocin (OT) and arginine vasopressin (AVP) have been reported to release PRL both in vivo and in vitro. The objectives of this study were 1) to compare the potencies of the PRL-releasing activities of OT and TRH using cultured anterior pituitary (AP) cells, and 2) to assess the PRL-releasing activity of naturally occurring neurohypophysial hormones and selected analogs. AP cells were incubated with peptides for 15 min, and medium PRL concentrations were determined by enzyme-linked immunosorbent assay. OT at 25, 100, and 400 nM increased PRL release by 110%, 175%, and 270%, respectively; higher concentrations (1600 and 6400 nM) did not cause a further increase in PRL release. TRH was 5-10 times more potent than OT on a molar basis. GH3 cells, a somatommamotroph tumor cell line, did not respond to OT and related compounds, but showed a similar responsiveness to TRH as AP cells. Twelve neurohypophysial peptides and selected analogs were incubated with AP cells, and their relative PRL-releasing activities were compared. OT and arginine vasotocin (AVT) showed the highest PRL-releasing activity. T4-G7-oxytocin, mesotocin, isotocin, lysine vasotocin, and AVP showed a moderate PRL-releasing activity, whereas, lysine vasopressin, desmopressin, tocinoic acid, pressinoic acid, and oxytocin free acid showed very low or no PRL-releasing activity. Coincubation of OT, AVT, or AVP with a specific OT receptor antagonist abolished their PRL-releasing activity. We conclude that 1) OT and related peptides are capable of stimulating PRL release in vitro, but their potencies are significantly lower than that of TRH; 2) unlike primary AP cells, GH3 cells are unresponsive to OT and related peptides; 3) AVT and AVP probably stimulate PRL release by acting via an OT receptor; and 4) the amino acid residues in positions 3 and 8 in the peptide chain and an amidated C-terminus are critical for the PRL-releasing activity of the neurohypophysial peptides.
Liu
J W
JW
Department of Anatomy and Cell Biology, University of Cincinnati School of Medicine, Ohio 45267.
Ben-Jonathan
N
N
D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D008969:Molecular Sequence Data; D010121:Oxytocin / Q000037:antagonists & inhibitors; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D010909:Pituitary Hormones, Posterior / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000378:metabolism
D010909:Pituitary Hormones, Posterior; D010121:Oxytocin; D011388:Prolactin