THE ROLE OF THE NEUROHYPOPHYSIS IN THE MILK-EJECTION REFLEX

1952 ◽  
Vol 8 (2) ◽  
pp. 148-161 ◽  
Author(s):  
B. A. CROSS ◽  
G. W. HARRIS

1. Nursing and suckling behaviour of rabbits is described, and evidence given that an active process of milk ejection ('let-down') occurs in this as in other species. 2. Intravenous injection of posterior pituitary extracts in anaesthetized rabbits resulted in ejection of milk from a cannulated teat duct. The threshold dose was about 5 mU. and maximal responses were produced by 200 mU. of extract. Whole posterior pituitary extract was more effective than the oxytocic fraction, which was in turn more effective than the vasopressor fraction. 3. Stimulation of the supraopticohypophysial (s.o.h.) tract in anaesthetized rabbits also resulted in ejection of milk from a cannulated duct. Kymographic records of this response were similar to those obtained after injection of appropriate doses of posterior pituitary extract. 4. Lesions in the s.o.h. tract in lactating rabbits caused a marked diminution in the quantity of milk obtained by their litters in standard suckling tests, and incomplete evacuation of the mammary glands. Intravenous injection of posterior pituitary extract (30–200 mU.) into the does immediately before nursing gave a marked increase in the amount of milk obtained by the young and complete evacuation of the mammary glands. Stimulation of the region of the s.o.h. tract in these animals failed to elicit milk ejection from cannulated teat ducts. 5. Rabbits with hypothalamic lesions that did not involve the s.o.h. tract showed a normal milk-ejection reflex when suckled by their young, and a milk-ejection response after electrical stimulation of the s.o.h. tract.

1953 ◽  
Vol 9 (1) ◽  
pp. 7-18 ◽  
Author(s):  
B. A. CROSS

1. Emotional inhibition of the milk-ejection reflex in rabbits is described. 2. Injection of 5–50 μg adrenaline intravenously into does before nursing interfered with milk ejection, as shown by the failure of the young to withdraw more than three-quarters of the normal yield of milk. Injection of 150 mU (=milliunits) 'Pitocin' immediately after the adrenaline did not restore normal milk ejection. 3. Intravenous injection of 5 μg adrenaline suppressed the milk-ejection response to 50 mU posterior pituitary extract in anaesthetized rabbits with cannulated teats, provided the injection of adrenaline preceded that of the posterior pituitary extract. The inhibitory effect had not entirely disappeared in 2 min. 50μg adrenaline prevented the occurrence of milk ejection for 3½ min. 4. Intravenous doses of 5 μg adrenaline, but not smaller amounts, inhibited the milk-ejection response to electrical stimulation of the supraoptico-hypophysial tract, if injected before stimulation or during the latent period of the response. When injected after the commencement of milk ejection 5 μg adrenaline was without effect, but 50 μg abolished the response. 5. Electrical stimulation of the posterior hypothalamus produced inhibition of the milk-ejection response to injected oxytocic extract, together with pupillary dilatation and exophthalmos. The inhibition closely resembled that resulting from injection of adrenaline. 6. It is concluded that one mechanism involved in the emotional inhibition of milk ejection is an activation of the sympathetico-adrenal system, resulting in antagonism of the action of the neurohypophysial milk-ejection hormone on the contraction process within the mammary gland.


1958 ◽  
Vol 149 (936) ◽  
pp. 330-336 ◽  

Following the demonstration by Strieker & Grüter (1928) of the lactogenic effects of anterior-pituitary extracts, the importance of the role of the pituitary in maintaining lactation was further emphasized by observations that removal of the pituitary in the lactating animal resulted in a rapid and complete cessation of lactation (for references, see Folley 1952). For a time it was generally assumed that the loss of the anterior pituitary was the causal factor in the cessation of lactation, but when the role of the posterior pituitary in milk ejection was established it became obvious that interference with the milk-ejection reflex could well be the cause of the failure of lactation after hypophysectomy. It therefore seemed desirable to repeat some of the earlier studies on the effect of hypophysectomy on lactation, in order to determine whether the restoration of milk-ejection by the regular administration of oxytocin would affect the results and possibly allow us to distinguish a failure of milk ejection from a failure of milk secretion. In this connexion it may be noted that reports on the maintenance of lactation after hypophysectomy, by administering anterior-pituitary preparations, have been remarkably few, and this lack of information possibly reflects the unsuccessful outcome of attempts which may have failed because milk ejection was not restored. At Shinfield we have studied the effect of hypophysectomy in the lactating rat, both in the presence and absence of adequate oxytocin therapy, and have confirmed that hypophysectomy results in a rapid and complete inhibition of milk secretion (see Cowie 1957), and there seems to be no reason to doubt that this will also be true for other species.


1985 ◽  
Vol 105 (1) ◽  
pp. 127-132
Author(s):  
C. M. Riggs ◽  
R. C. Sutherland ◽  
J. B. Wakerley

ABSTRACT Experiments were performed to reinvestigate the importance of mammary engorgement for activation of the milk-ejection reflex in the rat. Reflex milk ejection (measured by intramammary pressure recordings during a 2-h suckling test under anaesthesia) was compared in rats with engorged mammary glands (15-h separation from the pups, followed by sham-removal of milk) and in rats with drained mammary glands (15-h separation, followed by milk removal using a foster litter and exogenous oxytocin). In experiment 1, multiple small (2 mu.) doses of oxytocin were used for milk removal: these were effective in emptying the mammary glands and caused no subsequent impairment or change in sensitivity of the mammary response to oxytocin. Using this draining procedure, no significant differences were observed in either the number or relative amplitude of the milk ejections, or the occurrence of pup stretch reactions between engorged and drained rats. Similar results were seen in experiment 2, where an identical draining protocol was used, but the rats were pretreated with propranolol before the suckling test. In experiment 3, large (250 mu.) oxytocin doses were used for milk removal, as in previous studies. Again mammary draining had no effect on milk ejection in a subsequent suckling test (with propranolol pretreatment). However, the number of stretch reactions shown by the pups was significantly (P < 0·001) reduced from 8·6 ± 1·4/2 h to 1·9 ± 0·6/2 h. This effect probably related to long-term impairment of the oxytocin response of the mammary glands following the draining procedure, and could not be attributed to the draining per se. The dissociation of milk ejections and pup behavioural responses using this method of draining the glands explains previous reports, based on behavioural observations, that mammary draining profoundly disrupts milk ejection. It is concluded that mammary engorgement in fact has little influence on the activation of the milk-ejection reflex in the rat. J. Endocr. (1985) 105, 127–132


2019 ◽  
Vol 20 (14) ◽  
pp. 3507 ◽  
Author(s):  
Noriyuki Akahoshi ◽  
Hiroki Handa ◽  
Rintaro Takemoto ◽  
Shotaro Kamata ◽  
Masahide Yoshida ◽  
...  

Elevated plasma homocysteine levels are considered as a risk factor for cardiovascular diseases as well as preeclampsia—a pregnancy disorder characterized by hypertension and proteinuria. We previously generated mice lacking cystathionine γ-lyase (Cth) as cystathioninuria models and found them to be with cystathioninemia/homocysteinemia. We investigated whether Cth-deficient (Cth−/−) pregnant mice display any features of preeclampsia. Cth−/− females developed normally but showed mild hypertension (~10 mmHg systolic blood pressure elevation) in late pregnancy and mild proteinuria throughout development/pregnancy. Cth−/− dams had normal numbers of pups and exhibited normal maternal behavior except slightly lower breastfeeding activity. However, half of them could not raise their pups owing to defective lactation; they could produce/store the first milk in their mammary glands but not often provide milk to their pups after the first ejection. The serum oxytocin levels and oxytocin receptor expression in the mammary glands were comparable between wild-type and Cth−/− dams, but the contraction responses of mammary gland myoepithelial cells to oxytocin were significantly lower in Cth−/− dams. The contraction responses to oxytocin were lower in uteruses isolated from Cth−/− mice. Our results suggest that elevated homocysteine or other unknown factors in preeclampsia-like Cth−/− dams interfere with oxytocin that regulates milk ejection reflex.


1955 ◽  
Vol 12 (1) ◽  
pp. 29-37 ◽  
Author(s):  
B. A. CROSS

SUMMARY 1. Fifteen lactating rabbits were maintained on a regime of one daily nursing in which litter weights, milk yields and duration of nursing were recorded. 2. Sodium pentobarbitone anaesthesia blocked the milk-ejection reflex and prevented the removal of more than 15% of the full milk yield by the young. Intravenous injection of 50 mU oxytocin regularly restored normal milk removal; 10 and 20 mU did not. 3. In thirty-five out of forty-two experiments in which the does were suckled while under forcible restraint the amount of milk removed was reduced by 20–100%. In twenty-nine cases injection of 50 mU oxytocin restored normal milk removal. In the remaining six experiments this replacement therapy was fully effective only after the does had been anaesthetized. 4. Kymograph records of milk-ejection responses showed that normal milk removal was associated with a reflex milk-ejection response similar to that produced by 50 mU oxytocin, and incomplete milk removal with a reduced (=5 mU oxytocin) or absent milk-ejection response. Where injection of 50 mU oxytocin failed to restore normal milk removal in the conscious animal, the resulting milk-ejection response was reduced by an amount similar to that produced by injection of 1μg adrenaline. 5. The results indicate that, while activation of the sympathetico-adrenal system does occur, the main factor in emotional disturbance of the milk-ejection reflex is a partial or complete inhibition of oxytocin release from the posterior pituitary gland.


1962 ◽  
Vol 23 (4) ◽  
pp. 375-384 ◽  
Author(s):  
B. A. CROSS ◽  
I. A. SILVER

SUMMARY 1. Polarographic recording of pO2 from gold-plated needle electrodes inserted into lactating mammary glands of rabbits under light urethane anaesthesia gave resting values of 15–30 mm. Hg. Expelling the milk from distended glands raised the pO2 level. 2. Myoepithelial contraction (milk ejection) induced by i.v. injection of oxytocin lowered pO2 by an amount depending on the rise in intramammary pressure. 3. Surgical shock, spinal anaesthesia or i.v. injection of adrenaline depressed mammary pO2 and reduced the milk-ejection response to i.v. oxytocin. 4. When mammary pO2 was raised by O2 breathing, or lowered by N2 breathing, the milk-ejection response to i.v. oxytocin was not affected. 5. Electrical stimulation of the lateral and posterior hypothalamic areas reduced mammary pO2 and milk ejection in a way similar to i.v. adrenaline. Bilateral electrolytic lesions in these areas produced a sustained depression of mammary pO2. 6. It is concluded that the pO2 of mammary tissues gives a measure of capillary blood flow and that this, rather than the absolute pO2 level, determines the response of the myoepithelium to circulating oxytocin.


1968 ◽  
Vol 40 (2) ◽  
pp. 205-214 ◽  
Author(s):  
J. S. TINDAL ◽  
G. S. KNAGGS ◽  
A. TURVEY

SUMMARY Discrete portions of the afferent path of the milk-ejection reflex have been explored in the brain of the lactating guinea-pig. Both intramammary pressure and arterial blood pressure were recorded to detect release of oxytocin and vasopressin. It was found that the milk-ejection responses which occurred after electrical stimulation of the pathway in the midbrain and hypothalamus were caused by the release of oxytocin without detectable release of vasopressin. A mixture of oxytocin and vasopressin, in the ratio of approximately 3:1, was released only after electrical stimulation of the rostral tuberal region of the hypothalamus adjacent to the pituitary stalk. It is concluded that the afferent path in the brain of the guinea-pig studied is concerned with the preferential release of oxytocin from the neurohypophysis and that it is the pathway of the milk-ejection reflex.


1971 ◽  
Vol 50 (1) ◽  
pp. 135-152 ◽  
Author(s):  
J. S. TINDAL ◽  
G. S. KNAGGS

SUMMARY The effect of various types of surgical damage to the forebrain on the release of oxytocin in response to electrical stimulation of the discrete ascending milk-ejection reflex pathway in the mid-brain was investigated in 99 anaesthetized lactating guinea-pigs. Oxytocin release was measured by comparison of experimental milk-ejection responses with the response to i.v. injection of known amounts of synthetic oxytocin. Removal of the entire telencephalon, including cerebral cortex, hippocampi, amygdalae and forebrain rostral to the hypothalamus, did not affect the subsequent release of oxytocin after electrical stimulation of the pathway in the mid-brain, from which it was concluded that the reflex pathway within the forebrain is entirely diencephalic. Transection of the hypothalamus immediately rostral to the paraventricular (PV) nuclei was without effect, while transection immediately caudal to the PV nuclei blocked the release of oxytocin. Destruction of the PV nuclei by a radiofrequency lesion which spared the supraoptic (SO) nuclei blocked the release of oxytocin. Undercutting both PV nuclei so as to isolate them from the ventral hypothalamus blocked the release of oxytocin. Undercutting the PV nucleus ipsilateral to the stimulated side of the mid-brain blocked the release of oxytocin, while undercutting the contralateral PV nucleus had no effect. The PV nuclei, therefore, lie on the ascending path of the milk-ejection reflex, the SO nuclei do not, and, from the mid-brain forwards, the ascending pathway remains uncrossed. The course of the reflex pathway was traced rostrally from the mesodiencephalic junction by making narrow transverse knife-cuts and determining which cuts reduced or blocked the release of oxytocin after mid-brain stimulation. At this level, the pathway on each side of the brain is represented by separate dorsal and ventral paths and in the present study it was found that the ventral path is more important than the dorsal path in terms of oxytocin release. The ventral path passes forward in the medial forebrain bundle, in the far-lateral hypothalamus, while the dorsal path enters the posterior hypothalamus dorsally in the periventricular region at the top of the third ventricle and impinges on the thalamic reuniens nucleus. Shortly afterwards the dorsal path swings abruptly in the lateral direction to join the ventral path in the lateral hypothalamus. The reunited pathway then moves forward in this position until it is level with the PV nuclei, where it swings dorsomedially to relay with the lateral tip of the ipsilateral PV nucleus, and in doing so intermingles with the descending neurosecretory fibres from this nucleus.


1990 ◽  
Vol 127 (2) ◽  
pp. 257-263 ◽  
Author(s):  
A. Linden ◽  
M. Eriksson ◽  
S. Hansen ◽  
K. Uvnäs-Moberg

ABSTRACT Plasma levels of cholecystokinin were increased in response to suckling in lactating rats. Efferent electrical stimulation of the vagal nerve increased the concentration of cholecystokinin in plasma. Abdominal vagotomy was found to block the suckling-induced release of cholecystokinin. Furthermore, lesions to the lateral midbrain, which disrupt the oxytocin-mediated milk-ejection reflex, were shown to inhibit the increase in plasma cholecystokinin. These results show that the suckling-induced release of cholecystokinin into plasma in lactating rats is dependent upon the vagal nerves and the central neural structures concerned with milk let-down. Journal of Endocrinology (1990) 127, 257–263


1970 ◽  
Vol 47 (1) ◽  
pp. 45-53 ◽  
Author(s):  
PH. RICHARD ◽  
I. URBAN ◽  
R. DENAMUR

SUMMARY The milk-ejection reflex after different lesions of the sensory system was studied by mechanical milking of the ewe. Only animals with lesions which did not produce locomotor ataxia were investigated. Section of the dorsal tract of the spinal cord at different thoracic levels blocked the milk-ejection reflex. This was not due to postoperative shock, because the same type of lesion made at the sacral level was without effect. Moreover, unilateral section of this tract blocked the reflex when milking was limited to the ipsilateral mammary gland. At the cervical level, the interruption of the dorsal tract was ineffective, which can probably be explained by the existence, in sheep, of the spino-cervico-thalamic tract. The latter becomes ventral at the cervical level. Lesions of the lemniscal system in the mesencephalon (bilateral coagulation of the medial lemniscus) and in the thalamus (bilateral destruction of the ventral posterolateral nucleus) do not inhibit the milk-ejection reflex. The role of the spinal lemniscal system is discussed in relation to the work of others and to the electrophysiological results obtained by one of us. It is suggested that two sensory systems (lemniscal and extralemniscal) have to interact to induce the release of oxytocin evoked by the stimuli of mammary origin during milking.


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