Research dealing with hormones/growth factors in milk has progressed rapidly during the last 10 yr from their identification in milk to their regulation of various functions in the maternal organism and in the neonate. Many hormones, growth factors, and bioactive substances present in the maternal organism are present in colostrum and milk, often exceeding concentrations that occur in maternal plasma. Some appear in milk in different, sometimes multiple, forms from that found in maternal serum, reflecting to some extent synthesis and posttranslational processing by mammary tissue. Recent research has indicated that many milk hormones/growth factors survive the environment of the gut of the neonate, become absorbed into the neonatal circulation, and exert important functions in the neonate.

The present experiments tested the involvement of central catecholaminergic systems in the suckling-induced release of oxytocin (OT) during lactation in the rat. In the first experiment, female rats in midlactation were separated from their offspring for 4 h and then allowed to suckle their litters for 30 or 60 min or to remain nonsuckled. The turnover rates of norepinephrine (NE) and dopamine (DA) were calculated from the rate of decline after synthesis inhibition. Suckling decreased the turnover rate of DA in the median eminence and in the neurointermediate lobe of the pituitary gland. Suckling increased the turnover rate of NE in the rostral paraventricular and supraoptic nuclei, areas that contain most of the OT cells that project to the neural lobe of the pituitary, and in the interstitial nucleus of the stria terminalis, but not in the arcuate or caudal paraventricular nuclei, median eminence, or neurointermediate lobe. In a second experiment, midlactating females received intracerebral microinjections of the catecholamine neurotoxin 6-hydroxydopamine or of vehicle into the vicinity of the paraventricular and supraoptic nuclei 1 week before a suckling test. The release of OT was completely prevented in 6-hydroxydopamine-treated animals, and NE was significantly decreased in the paraventricular, supraoptic, and arcuate nuclei. In a third study, the increase in plasma OT in response to suckling was prevented by stimulation of DA receptors with bromocriptine, while blockade of DA receptors with domperidone significantly increased plasma OT levels in nonsuckled lactating rats. These results suggest that suckling stimulation activates the noradrenergic innervation to the rostral paraventricular nucleus and to the supraoptic nucleus, which exerts an excitatory influence on the release of OT and decreases activity of the tuberohypophyseal DA system, which provides a tonic inhibitory influence over the secretion of OT.

The present studies were designed to investigate whether prolactin (PRL) influences the secretion of oxytocin (OT) in lactating rats, and to test whether the previously reported inhibitory and stimulatory effects of dopamine-2 (D-2) agonists and antagonists, respectively, on OT release might be secondary to their respective inhibitory and stimulatory effects on the release of PRL. Intravenous administration of either rat (r) or ovine (o) PRL to lactating, nonsuckled rats increased basal plasma concentrations of OT. rGH was ineffective, but administration of oGH did produce some stimulation of OT release. Both oPRL and rPRL significantly enhanced the electrical stimulation-induced release of OT from isolated stalk-neurointermediate lobes, in vitro, without affecting the basal release of the peptide. oGH was ineffective on basal or stimulated in vitro OT release, and neither hormone altered basal or stimulation-induced release of vasopressin from these tissues. Both rPRL and oPRL reversed the inhibitory effect of the D-2 dopamine agonist bromocriptine. Immunoneutralization of circulating PRL with a highly specific antiserum abolished the increases in OT in response to either suckling or to administration of the D-2 dopamine antagonist domperidone. These findings suggest that (1) an action of PRL released by suckling may be of physiological importance in promoting the release of OT in lactating rats; (2) that PRL may increase OT release, at least in part, through a stimulatory action on the neural lobe, and perhaps directly on OT-containing neurosecretory nerve endings, and (3) that the previously reported inhibitory effect of D-2 dopamine receptor stimulation, and the stimulatory effect of a D-2 dopamine antagonist on OT release may be secondary to their analogous actions on the release of PRL.

We have compared the effectiveness of TRH and a rat hypothalamic PRL-releasing factor (PRF; previously incubated with rat serum to destroy TRH) in stimulating the release of PRL into the plasma of conscious lactating rats when injected before and after pituitary PRL had been depleted and transformed into releasable PRL by 10 min of suckling. TRH (1.25 microgramsss) and PRF [equivalent to 2.5 stalk median eminence (SME) fragments] each caused a small increase (38 and 30 ng, respectively) in the plasma PRL concentration within 10 min when injected into nondepleted mothers. The levels then fell quickly. Suckling, by comparison, caused a sustained 175 ng/ml increase above basal levels. Though PRL depletion occurred, as expected, as a result of suckling, there was no measurable depletion within the pituitaries of TRH- or PRF-injected rats. By contrast, the iv administration of TRH (doses ranging from 2-250 ng) and hypothalamic PRF (doses ranging from 0.2-1.0 SME equivalent) after depletion-transformation had been effected by 10 min of suckling resulted in a rapid and, in most instances, a sustained elevation in the plasma PRL concentration comparable to that seen after suckling. Dose-response relationships, though, were not clearly evident with either PRF or TRH. Neither saline, 1.25 microgram TRH previously incubated in serum, 50 mU oxytocin, 1 microgram dopamine, 25 microgram LHRH, nor an extract of cerebral cortex prepared in the same manner as hypothalamic TRH caused plasma PRL to rise after PRL depletion. We conclude that TRH and possibly a separate hypothalamic PRF have a stimulatory action upon the releasable, but not upon the depletion-transformation, phase of PRL secretion in the lactating rat.

Research dealing with hormones/growth factors in milk has progressed rapidly during the last 10 yr from their identification in milk to their regulation of various functions in the maternal organism and in the neonate. Many hormones, growth factors, and bioactive substances present in the maternal organism are present in colostrum and milk, often exceeding concentrations that occur in maternal plasma. Some appear in milk in different, sometimes multiple, forms from that found in maternal serum, reflecting to some extent synthesis and posttranslational processing by mammary tissue. Recent research has indicated that many milk hormones/growth factors survive the environment of the gut of the neonate, become absorbed into the neonatal circulation, and exert important functions in the neonate.