Endocrinology, Vol 125, 61-67, Copyright © 1989 by Endocrine Society
Presence of calcitonin-like peptide in rat milk: possible physiological role in regulation of neonatal prolactin secretion
GV Shah, B Kacsoh, R Seshadri, CE Grosvenor and WR Crowley
Department of Pharmacology, University of Tennessee, Memphis 38163.
Previous results have shown that salmon calcitonin (sCT), a peptide in rat
brain and pituitary gland, inhibits basal and TRH-stimulated PRL release
and reduces PRL mRNA levels in isolated anterior pituitary cells of adult
rats in culture. Rat milk contains a variety of neuropeptides and hormones,
some of which are absorbed in bioactive form to exert endocrine influences
in the developing offspring. The present studies were undertaken to
investigate whether a CT-like peptide is present in rat milk. Circulating
PRL levels in neonatal rats are low, and there is an abrupt increase in the
basal secretion of this hormone at weaning. A second objective was to
examine whether CT plays a role in the regulation of PRL secretion in
neonatal animals. A sensitive and specific RIA for sCT was developed and
used to assay rat milk on various days of lactation for sCT-like
immunoreactivity. sCT- like activity was present in the water-soluble
(infranatant) fraction of milk throughout lactation in concentrations as
high as 1589 pg/ml. There were no statistically significant differences in
immunoreactive levels of the peptide in milk samples from different days of
lactation. sCT-like immunoreactivity in rat milk infranatant coeluted with
synthetic sCT on reverse phase HPLC, and these HPLC fractions inhibited
basal PRL release when added to cultures of anterior pituitary cells. This
inhibition of PRL release by the sCT-immunoreactive HPLC fractions was
comparable to that exerted by equivalent concentrations of synthetic sCT.
Newborn rats were injected sc with 10 microliters normal rabbit serum or
anti-sCT serum from the day of birth until postpartum day 10. The rats were
killed on day 11, and their sera were analyzed for PRL. Anti-sCT-injected
rats showed a significant increase in serum PRL levels compared to those in
untreated or normal serum-treated rats. These results demonstrate that a
CT-like peptide, which is a potent inhibitor of PRL release, is present in
rat milk throughout lactation, and that passive immunization with a highly
specific anti-sCT serum leads to an increase in serum PRL levels in
neonatal rats. CT, possibly of milk origin, may be a physiologically
relevant PRL-inhibiting factor during the neonatal period.