Search Results

You are looking at 1 - 10 of 33 items for

  • Author: J. S. TINDAL x
  • All content x
Clear All Modify Search
Restricted access

J. S. TINDAL

SUMMARY

The daily administration of ergotamine (0·2 mg) or dihydroergotamine (0·2 mg) to rats from the 12th to 21st day of pregnancy caused considerable pup mortality. This appeared to be due to a toxic effect in utero rather than an inhibition of lactation.

The daily administration of ergotamine (0·2 mg) to rats from 2nd to 13th day of lactation caused a significant reduction in growth-rate of the pups. There was also a significant reduction in food intake by the lactating rats. Daily administration of dihydroergotamine (0·2 mg) to rats over the same period had no effect on lactational performance.

When studied by the paired-feeding technique, daily administration of ergotamine (0·4 mg) had no effect on lactational performance in the rat.

These findings appear to contradict previous reports, and have been discussed in relation to them.

Restricted access

J. S. TINDAL

SUMMARY

A single intravenous injection of reserpine (1 mg/kg), given either on day 15 of pseudopregnancy or after priming with 0·2 mg oestradiol-17β daily for 10 days, resulted in lactogenesis in virgin female rabbits of the New Zealand White breed. This finding is in contrast to earlier negative results with Dutch rabbits in this laboratory. Thymus weight dropped significantly after reserpine in the pseudopregnant animals, but reserpine did not lower the thymus weight in oestradiol-primed rabbits to an extent greater than could be accounted for by the effect of the oestrogen alone.

From these results, it is concluded that there is a breed difference in the lactogenic response of New Zealand White and Dutch rabbits to reserpine.

Restricted access

J. S. TINDAL and A. YOKOYAMA

SUMMARY

A quantitative study has been made of the effects of hypophysectomy on the growth of the young goat kid. Four pairs of castrated male twins and two pairs of intact female twins were used. The heavier member of each pair was hypophysectomized at the age of 25–39 days and animals were killed when 8½–9½ months old. Hypophysectomy significantly retarded the rate of body growth and prevented normal development of the ruminal mucosa. The thyroid glands of the hypophysectomized animals were more inactive than those of the controls, the adrenal cortices were less well developed, the livers were vacuolated, and in the females the uteri and vaginae were smaller. One of the two hypophysectomized females was found to be an intersex, with 'ovaries' composed of testicular tissue, while the ovaries of the other hypophysectomized female contained Graafian follicles.

Restricted access

J. S. TINDAL and G. S. KNAGGS

SUMMARY

Rabbits were implanted unilaterally with a bipolar electrode in the forebrain, and approximately 10 days later pseudopregnancy was induced by i.v. injection of human chorionic gonadotrophin. One week later the rabbits began receiving electrical stimulation with square-wave pulses through the implanted electrodes for two periods of 15 min daily for 11 days. At autopsy on the 12th day the mammary glands were inspected for the occurrence of lactogenesis and sites of electrode tips in the brain were determined histologically. In a preceding study a prolactin-release path, believed to be that normally activated by the suckling stimulus, had been traced from the mid-brain as far rostral as the posterior hypothalamus, and in the present work, lactogenesis, indicating release of prolactin, occurred after electrical stimulation of this same region in the posterior hypothalamus, between the third ventricle and the mammillo—thalamic tract. Further rostrally, effective stimulation sites were found in the medio-dorsal hypothalamus, in the farlateral hypothalamus within the medial forebrain bundle, and in the lateral and medial preoptic area. Sites extended caudally from the last area to the medial anterior hypothalamus. Passing rostrally from the lateral preoptic area, effective sites occurred in, and ventral to, the external capsule, in the claustrum and in the adjacent orbitofrontal cortex which yielded the two maximum lactogenic responses observed in the stimulated group. The role of these rostral structures, in particular the orbitofrontal cortex, is not yet clear, nor is the final mechanism mediating prolactin release, although the results suggest that the ascending pathway for prolactin release approaches the medial hypothalamus by way of the preoptic area. The presence of control electrodes in the brains of pseudopregnant rabbits was found to cause lactogenesis when their tips were in structures associated with prolactin release, as determined from the stimulated group of animals. It was concluded, therefore, that electrical stimulation may have been unnecessary in this work and that the physical irritation caused by the presence of the electrode tip in appropriate neuronal systems may be a sufficient stimulus per se to be used for tracing prolactin-release pathways in the brain.

Restricted access

J. S. TINDAL and G. S. KNAGGS

SUMMARY

Rabbits in pentobarbitone anaesthesia were implanted bilaterally with a pair of monopolar electrodes in the brainstem. Approximately 10 days after the operation, pseudopregnancy was induced by i.v. injection of human chorionic gonadotrophin, and 1 week later the rabbits received electrical stimulation with square-wave pulses through the implanted electrodes for two periods of 30 min. daily for 11 days. At autopsy on the following day the mammary glands were inspected for occurrence of lactogenesis and sites of electrode tips in the brain were determined histologically. Lactogenesis, indicating release of prolactin, occurred when electrical stimulation had been applied to sites in the lateral mesencephalic tegmentum and further forward in a region medio-ventral to the medial geniculate body. Passing rostrally, the pathway moved medially and then forwards in association with the extreme rostral central grey matter, and was traced as far forward as the posterior hypothalamus where sites were found close to, but not involving, the mammillo-thalamic tracts.

When compared with our previous studies on the afferent path of the milk-ejection reflex in this species, the ascending path for release of both oxytocin and prolactin appears to be the same in the mesencephalon. However, whereas the ascending path for oxytocin release bifurcates on each side into dorsal and ventral paths which reunite in the posterior hypothalamus, that for prolactin release appears to follow only the dorsal path, since stimulation of the subthalamus, through which the ventral path passes, was ineffective. It is proposed that the pathway traced in the present study represents the mesencephalic and posterior diencephalic route by which impulses initiated by the suckling stimulus attain the hypothalamus to evoke release of prolactin from the adenohypophysis.

Restricted access

J. S. TINDAL and 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.

Restricted access

J. S. TINDAL and G. S. KNAGGS

SUMMARY

When the afferent pathway of the milk-ejection reflex, which we had previously reported, was surgically severed bilaterally in the mid-brain of the lactating rabbit, the reflex release of oxytocin in response to suckling was blocked for up to 11 days; unilateral severance did not block the reflex. The position and discrete nature of the pathway were also further substantiated by electrical stimulation experiments in acute studies in the anaesthetized rabbit. Some animals, however, did not release oxytocin in response to stimulation of the pathway. Furthermore, whereas stimulation of this reflex pathway in the guinea-pig brain at intervals of a few minutes evokes release of oxytocin after each stimulation, in the present study the release of oxytocin in the rabbit in response to repeated electrical stimulation was either progressively attenuated or did not occur at all after the initial release. There appears, therefore, to be a powerful overriding central inhibitory mechanism in the rabbit which can prevent release of oxytocin, even when the appropriate stimulus for release is applied.

Restricted access

A. T. COWIE and J. S. TINDAL

SUMMARY

Experiments to determine the pituitary hormones necessary for the maintenance of lactation in the rat in the absence of either the anterior lobe of the pituitary or the entire pituitary are described.

The anterior pituitary or the whole of the pituitary was removed on the 12th day of pregnancy and prolactin (25 i.u. twice daily) plus adrenocorticotrophic hormone (ACTH) (2 i.u./day) was given to the animals from parturition to the 10th day of lactation inclusive. The lactational performances of the two operated groups of rats, as judged by the litter-growth indices, were 53% (anterior lobectomy) and 43% (hypophysectomy) of normal.

The milk-ejection reflex was completely restored in the anterior-lobectomized rats by the time of parturition, but the hypophysectomized rats required a further 2 days before milk ejection appeared to be normal.

Our experiments confirm that prolactin and ACTH are two important factors in the maintenance of milk secretion in the rat. Since only partial restoration was achieved, however, it is clear that other factors, presumably of anterior-pituitary origin, are required for the full restoration of lactation.

Restricted access

A. T. COWIE and J. S. TINDAL

SUMMARY

The mean survival period of twelve goats after adrenalectomy was 7·8±1·2 days. Adrenalectomy resulted in a progressive rise in the concentration of K and a fall of Na in the plasma. In the lactating goat there was a rapid inhibition of milk secretion and the concentration of K in the milk fell, while that of Na rose slightly as the yield dropped. Partial to complete maintenance of lactation was achieved in five lactating goats after adrenalectomy by implanting tablets of cortisone (or cortisone acetate) and deoxycorticosterone acetate (DCA), a daily absorption of at least 6–12 mg cortisone (or its acetate) and 2·5 mg DCA being required. DCA was the more critical component of the combination. During replacement therapy, when the daily milk yield had become relatively steady, the composition of the milk (fat and solids-not-fat percentages) and the Na and K concentrations in the milk were within the pre-operative ranges, but during the periods of adrenal insufficiency, when the milk yield declined, there was a concomitant rise in milk-fat percentage and a fall in milk K. These changes, however, also occurred when the milk yields fell from other causes and so they may not be directly attributable to the lack of adrenal steroids.

Restricted access

A. T. COWIE and J. S. TINDAL

SUMMARY

Five adult goats were hypophysectomized during lactation; within 10 days their milk yields dropped to a fifth or less of the preoperative levels.

The daily milk yield of one of these goats was increased from 10 to 288 ml. by giving daily injections of ox anterior-pituitary extract; the yield of a second goat was increased from 110 to 1315 ml. by daily injections of sheep anterior-pituitary extract. Treatment of the three other goats with purified anterior-pituitary hormones, corticoids, insulin and triiodo-l-thyronine increased their milk yields from 230, 10 and 45 ml./day to 1480, 1320 and 270 ml./day, respectively.

Milk secretion was induced in the right udder-half of a sixth animal—which had been hypophysectomized in mid-pregnancy and had aborted—by the local injection of prolactin into the parenchyma of the right udder-half plus the systemic injection of somatotrophin; general lactation was subsequently induced and maintained by systemic treatment with prolactin, somatotrophin, adrenocorticotrophin, corticoids, insulin and triiodo-l-thyronine. The maximum daily yield of the animal was 625 ml.

Prolactin and somatotrophin appear to be major components of the lactogenic and galactopoietic complexes in the goat, but further study is required to determine their relative importance and to confirm a preliminary observation that lactation may proceed in the hypophysectomized goat at least for a time by treatment with hormone combinations which include somatotrophin but not prolactin.

A marked increase in water intake of one hypophysectomized goat appeared to be associated with the administration of somatotrophin.

The possibility of species specificities existing in relation to prolactin are discussed.