Clark E. Grosvenor

Effect of Lactation upon Thyroid Secretion Rate in the Rat.

Summary 1) Thyroid hormone secretion rate (TSR) was determined in lactating and non-lactating rats by administration of graded levels of L-thyroxine and measuring by radioiodine technics, subsequent suppression of thyroidal I131 output. 2) The average TSR of 2.2 μg/100 g L-thyroxine for lactating rats during the period of intense lactation (8–14 days postpartum) was significantly greater than the average of 1.3 μg/100 g for non-lactating rats of the same strain, age and weight range. These data are in accord with the concept that a hyperthyroid state is generally desirable for optimal milk secretion.

Release and restoration of pituitary lactogen in response to nursing stimuli in lactating rats.

Summary 1) The effects of nursing stimuli upon release and subsequent restoration of lactogenic hormone from the hypophysis has been studied in 2 strains of lactating rats on 14th day postpartum. 2) Wistar lactating rats produced litters which, when 14 days old, were almost as heavy as those of the much larger Sprague-Dawley mothers. There was 15% more pituitary gland/100 g in Wistar rats which, after 10 hours isolation of mother and litter assayed 30% more lactogen than pituitaries of Sprague-Dawley mothers (3.50 and 2.44 units/100 g, respectively). The Reece-Turner pigeon intradermal method of assay was used. Following 30 minutes nursing there was a greater discharge of lactogen (33%) in Wistar (1.16 units/100 g) than in Sprague-Dawley rats (0.78 unit/100 g). About one-half prenursing level was restored in both strains within 2 1/2 hours postnursing but in one strain tested (Sprague-Dawley) restoration to prenursing level did not occur even 9 1/2 hours postnursing. The influence of amounts of lactogen released in the two strains is discussed in relation to lactational performance.

Evidence for Adrenergic and Cholinergic Components in Milk Let-Down Reflex in Lactating Rat.

Summary The amount of milk obtained by litters of lactating rats treated with various ergot alkaloids, Dibenamine or atropine, was compared with control values previously obtained. All ergot drugs tested significantly blocked the let-down response. Methylergo-novine (Methergine) was the most potent inhibitor, followed by the dihydroergotoxine complex (Hydergine) and dihydroergotamine (DHE 45), in that order. Results indicate action on central nervous system is probably responsible for some, or perhaps all, milk letdown inhibitory action of ergot drugs. This observation was based primarily on results with Methergine, a non-sympatholytic compound. Dibenamine evoked symptoms of central excitation which persisted for 30-45 minutes after injection though milk let-down was not inhibited in those animals who nursed during this period. Milk let-down, however, was significantly inhibited when the drug was injected 2 hours prior to nursing, after which time adrenergic blockade has occurred. Atropine induced a highly significant blockade of the let-down response when injected 150-220 minutes before nursing, but failed to block the response when administered 15-60 minutes before nursing. Oxytocin administered after any of these drugs restored normal milk let-down, indicating blockade was central rather than peripheral. Since Dibenamine. Hydergine and DHE 45 are powerful adrenergic blocking agents and atropine a cholinergic blocking agent, it is postulated both adrenergic and cholinergic links are present in the neurohumoral arc responsible for discharge of oxytocin from the posterior pituitary gland.

Effect of growth hormone and oxytocin upon milk yield in the lactating rat.

Summary (1) We have investigated the effect of growth hormone (GH) and oxytocin alone, and in combination, upon lactation in the rat. Amount of milk obtained by a litter of 6 during 30 minutes nursing on day 14 postpartum, expressed as percent litter body weight, was used as the index of response. (2) Control yields averaged 3.8% with normal distribution. Removal of milk with aid of .1 USP unit/kg oxytocin i.v. resulted in 50% higher yield with more uniformity among individual values. (3) GH injected subc., from days 7-13 at dose of 1 mg/rat/day evoked a 41.1% increase in milk yield. Yields obtained in GH-treated lactating rats with aid of oxytocin were greater and more uniform than with GH or oxytocin alone. The significance of this is discussed. (4) GH had no effect upon pituitary, thyroid or adrenal weight/100 g body weight. GH caused a significant increase in percent weight gain of mothers but not their litters. Litter growth rate as an index of lactation in the rat is discussed.

Thyroid hormone and lactation in the rat.

Summary We have investigated effects of l-thyroxine alone, and in combination with oxytocin and growth hormone (GH) upon lactation in the rat. Amount of milk obtained by a litter of 6 during 30 minutes nursing on day 14 postpartum, expressed as percent litter body weight, was used as the index of response. 1. 3.0 μg/100 g/day l-thyroxine, a level equal to the highest daily thyroid secretion rate previously observed, injected daily from days 7–13, increased average milk yield 37%. That obtained with aid of oxytocin, to insure maximum milk removal, in rats injected for 7 days with l-thyroxine alone, or with 1 mg GH/day, was increased 63.2 and 73.7%, respectively. With addition of each hormone there resulted also a progressive reduction in variation among individual milk yields. It is suggested suboptimal thyroid hormone secretion may limit intensity of milk secretion in many lactating rats. 2. Increased milk secretion, obtained with l-thyroxine with or without GH was not reflected in significant increases in litter growth as analyzed by percent weight gain during period of treatment. Thyroxine had no adverse effect on maternal body weight. Increase in maternal weight due to GH was offset by simultaneous treatment with thyroxine. 3. Thyroxine induced a significant increase in maternal pituitary gland weight which was offset when administered with GH. Adrenal gland weight was significantly increased in lactating rats injected with l-thyroxine plus GH but was unaffected by l-thyroxine alone.

Ergotamine, Oxytocin and Milk Let-Down in Lactating Rat.∗:

Summary 1. The quantity of milk secured by litters of lactating rats treated with ergotamine 10 minutes before nursing was significantly less than that obtained by control offspring. Oxytocin administered before or after ergotamine restored normal milk letdown. 2. Topical application of ergotamine to living rat mammary tissue resulted in arteriole constriction but did not interfere with normal myoepithelial contraction induced by oxytocin. 3. Results indicate ergotamine does not inhibit milk let-down through vasoconstriction of mammary blood vessels thus prohibiting access of oxytocin to effector myoepithelium. Rather, a competition between ergotamine and oxytocin for the effector tissue or a neural block inhibiting release of oxytocin by posterior pituitary gland seem more probable.

A method for evaluation of milk "let-down" in lactating rat.

Summary A method for evaluation of milk “let-down” in mature lactating rats on 14th day postpartum is described. Amount of milk obtained by litters of 6 young after 30 minutes nursing expressed as percent litter body weight is used as criterion of response. Results obtained follow a normal distribution pattern with a mean value of 3.8 ± .19. The results of this study may serve as a basis for evaluating data from experimental alteration of milk “let-down” in lactating rats.

Effect of Estrogen upon Thyroxine Secretion Rate in Intact Female Rats.

Summary The effect of various levels of estradiol benzoate (E.B.) upon thyroxine secretion rate (TSR) has been studied in young mature female rats. A dose of 3.6 μg/day E.B. caused significant increase of 35.5% in TSR over average control value of 1.24 μg/100 g/day l-thyroxine while 1, 15 or 50 μg/day had no effect. In another experiment, body weight and thyroid weight/100 g were not affected by injecting 1 or 3.6 μg/day E.B. for 5 days. Thyroid weight/100 g was significantly increased while appetite and body weight were markedly reduced following 15 or 50 μg/day for same period. Pituitary weight/100 g was significantly increased in all but the 1 μg/day group. Adrenal weights/100 g were lower in all groups with significant depression occurring in 50 μg/day group. These data are discussed in relation to stimulation or depression of thyroid activity by estrogen.

Lactogenic hormone requirements for milk secretion in intact lactating rats.

Summary A technic is described for determination of amount of lactogenic hormone required for milk secretion in intact lactating rats. Rats were isolated from their litters for 12 hours on day 14 postpartum then deeply anaesthetized with 4.5 mg/100 g Nembutal and all milk withdrawn by 9 young with aid of oxytocin. With lactogenic hormone discharge blocked and mammary glands empty, significantly less milk (.85 g/100 g maternal body weight) was obtained following a 2nd 12-hour isolation period in comparison with 2.92 g/100 g for unanaesthetized controls. Injection of .5, 1, 1.5 or 2 mg lactogenic hormone during 2nd isolation period significantly restored milk yield approximately 70%. Yields were, nevertheless, significantly less than controls. No greater milk yield resulted from injection of more than 1 mg lactogen. These data indicate that lactogen is necessary for maintenance of milk secretion in intact rats and strongly imply that since lactogen alone was incapable of restoring milk secretion 100%, other pituitary hormones are necessary for full milk secretion and perhaps might be susceptible to discharge by nursing stimuli.

Estimation of Amount of Oxytocin Released as Result of Nursing Stimuli in Lactating Rat.

Summary We estimated amount of oxytocin required for normal milk let-down in lactating rats. This was determined by injecting various doses of oxytocin i.v. into anaesthetized mothers while young were actively sucking and comparing weight of milk obtained by young expressed as percent litter body weight with normal values. Nembutal (3 mg/100 g) blocked milk let-down reflex and prevented removal of milk by the young .05 USP/kg oxytocin restored normal milk withdrawal; .02 USP/kg did not. Much greater yields were obtained with .1 USP/kg. Milk flow commenced with all doses after latent period of 5–10 seconds and lasted 4–5 minutes. It is concluded that normal 14 day postpartum lactating rats vary in amount of release of oxytocin following nursing stimuli from less than .02 to .1 USP/kg.