No abstract

In several species the myometrium is quiescent shortly before parturition. At this time high titres of relaxin are present in the plasma and there is evidence that the hormone has a direct inhibitory action on the uterine muscle. Relaxin could also contribute to uterine quiescence by inhibiting oxytocin release. To determine whether relaxin has a central action on the release of oxytocin, we have studied the effect of intravenous injections of porcine relaxin on milk ejection in the anaesthetized lactating rat. We report that reflex milk ejection was suppressed by relaxin in a dose-dependent manner, the onset of inhibition being rapid and lasting from 10 to 60 min. After the period of inhibition the normal temporal pattern of reflex milk ejection was resumed. Mammary sensitivity to exogenous or endogenous oxytocin was reduced by relaxin but not sufficiently to explain the effects observed. Furthermore, relaxin (1 microgram per rat) injected into the cerebral ventricles profoundly disturbed the pattern of reflex milk ejection without affecting the response of the mammary gland to oxytocin. These results suggest a novel role for relaxin within the central nervous system. The site in the brain at which the effects of relaxin are exerted remains unknown.

SUMMARY1. Extracellular electrical recordings were taken from twenty antidromically identified paraventricular neurones in unanaesthetized, unrestrained rabbits. Neuronal activity was correlated with nursing behaviour of the doe and responses of the young during suckling.2. Magnocellular neurones were divided into two groups on the basis of their activity in suckling. Group 1 (n = 14) showed several discrete bursts ofhigh-frequency activity whilst neurones in group 2 (n = 6) did not.3. Neurones in group 1 showed 5-9 bursts of high-frequency activity in suckling. Each burst lasted 1-4 s and represented a 3-10-fold rise in the discharge of the cell. These units were classified as oxytocinergic, as their stereotyped activation preceded bouts of sucking behaviour of the young indicative of milk ejection. All fourteen cells continued to show intermittent bursts of neurosecretory activity for up to 20 min after nursing terminated. This pattern of discharge followed grooming behaviour of the doe.4. In contrast, neurones in group 2 (n = 6) showed no high-frequency activity in suckling. They showed a significant fall in their discharge frequency compared with pre-suckling values (P < 0-05; Student's t test) and a significant (P < 0-05) lengthening ofthe modal interspike interval. They were classed as potential vasopressin-producing cells.5. Control recordings were taken from thirty-two neurones which could not be antidromically driven. The recording sites were shown histologically to be in the lateral hypothalamic area. These cells showed a significant fall in their discharge frequency (P < 0 05) and a significant increase (P < 0-01) in the modal interval during suckling.6. Cross-correlation studies of the activity, recorded from one electrode, of groups of neurones clustered around a single hypothalamic neurone suggest that bursting discharge from the putative oxytocin neurones in suckling is accompanied by the synchronous activation of some of the surrounding magnocellular units.

Nursing behaviour and reflex milk ejection were studied over 257 suckling periods in 26 Californian rabbits. Detailed plasma profiles of oxytocin were obtained for 161 suckling periods in 16 animals. Plasma oxytocin was detected by radioimmunoassay in serial samples of 0.2 ml blood collected during nursing. Oxytocin titres were below the lower limit of the assay (5 pmol/l) before suckling, and started to rise at a rate of 2.8 +/- 0.8 (S.D.) pmol/l per s 10-30 s after the onset of suckling. Peak levels of hormone were 345 +/- 113 pmol/l and were attained towards the end of nursing. In 33 of these experiments simultaneous records of activity from oxytocin neurones were taken whilst chronically sampling the blood. Each neurone gave an average of seven bursts of neurosecretory activity in suckling. Onset of this bursting pattern of discharge began 5-24 s before the rise in plasma oxytocin was detected. Oxytocin neurone activity alone was monitored in a further 55 suckling periods in eight rabbits. A marked relationship between the duration of suckling period, milk yield, peak oxytocin levels and the length of neurosecretory bursts was demonstrated over the course of lactation. All four parameters increased in parallel from day 1 to reach maximal values on days 15-20 of lactation then started to wane until the doe ceased nursing her litter on days 25-27 of lactation.

No abstract