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P. E. HARTMANN

SUMMARY

Mammary secretion (1·2–2·0 ml) was collected from the milk sinus of each mammary gland (quarter) of two pregnant heifers and eight pregnant cows (dry period 49–229 days), first at weekly intervals from 40 days before parturition, then with increasing frequency as parturition approached. The progressive changes in the concentration of lactose, glucose, casein, non-casein protein and fat in the mammary secretion were determined. Calves were separated from the cows immediately after birth and the yield and composition of milk from individual quarters were determined for 5 days after parturition. Two quarters (milked quarters) of each of a further five cows were milked throughout pregnancy, while the other two quarters (unmilked quarters) of each cow were allowed to involute (dry off) 63– 104 days before parturition. Small samples (5–10 ml) of secretion were collected from the unmilked quarters, first at weekly intervals after drying off and then every second day from 10 to 15 days before parturition. On the days that the unmilked quarters were sampled, corresponding composite milk samples were collected from the milked quarters and the progressive changes in the yield of milk, lactose and fat were determined. The changes in the concentration of lactose and glucose in the mammary secretion, during drying off in late lactation, were determined in an additional five cows.

In most cows allowed a usual dry period, and in the unmilked quarters of cows in which two quarters were milked throughout pregnancy, the concentration of lactose gradually increased from about 8 to 12 days before parturition to reach levels of about half those found in normal milk just before parturition. However, in some cows the concentration of lactose was low until 1–2 days before parturition and then increased abruptly, whereas in others the concentration of lactose increased slowly from as early as 32 days before parturition. A further rapid increase in the concentration of lactose in the mammary secretion occurred between 0 and 4 days before parturition in all cows. This latter increase was accompanied by an abrupt increase in the yield of milk, lactose and fat in the milked quarters of the cows in which two quarters were milked throughout pregnancy. These observations suggest that the initiation of lactation in the cow develops in two phases, a limited secretion of milk constituents occurs in late pregnancy and then 0–4 days before parturition copious secretion (lactogenesis) occurs.

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P. E. HARTMANN, P. TREVETHAN and J. N. SHELTON

SUMMARY

The concentrations of lactose and progesterone were determined in mammary secretion and blood plasma, respectively, collected from ten ewes at daily intervals from 30 days before to 10 days after parturition. An initial increase in the concentration of lactose in the mammary secretion occurred as early as 30 days before parturition and was not related to changes in the concentration of progesterone in the peripheral plasma. On the other hand, there was a rapid fall in the concentration of progesterone in the peripheral plasma from 1 to 4 days before parturition and this fall was closely related to a second rapid increase in the concentration of lactose in the mammary secretion. The foetuses were removed from an additional 12 ewes by Caesarean section at 144 days of gestation; three ewes received no hormone therapy; three ewes received 62·5 mg progesterone/12 h for 5 days; three ewes received 2·0 mg oestradiol at 12, 24 and 36 h respectively after surgery; three ewes received both progesterone and oestrogen therapy. Whereas progesterone inhibited the increase in milk yield and lactose concentration after Caesarean section, progesterone and oestrogen in combination inhibited only the increase in milk yield. These results suggest that progesterone withdrawal initiates lactogenesis in the ewe.

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A. T. COWIE, P. E. HARTMANN and A. TURVEY

SUMMARY

Twenty-one rabbits were hypophysectomized during the second week of lactation. Hypophysectomy inhibited milk secretion within 3–7 days. Restoration of the milk yield to pre-operative levels was obtained when daily injections of either sheep prolactin (50 or 100 i.u.) or human growth hormone (HGH) (2·5 or 5 mg.) were administered; partial recovery of the milk yield was obtained with 25 i.u. sheep prolactin/day or 1·25 mg. HGH/day. Neither bovine growth hormone (BGH), adrenocorticotrophin (ACTH) nor cortisol acetate had any significant restorative effects on milk secretion or synergistic effects when combined with sheep prolactin or HGH. The probable development of immune responses to sheep prolactin and HGH was observed. After hypophysectomy, changes in milk composition were found which were similar in trend to the more gradual normal changes observed in late lactation. Sheep prolactin and HGH restored the composition of the milk as well as the yields to normal levels, and both hormones caused rapid increases in lactose yields.

The pigeon crop-stimulating potency of the HGH preparation was low (equivalent to 3·7 i.u. sheep prolactin/mg.), yet its lactogenic and galactopoietic potencies were high thus emphasizing the unreliability of assessing the mammotrophic potencies of HGH preparations in birds.

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P. E. HARTMANN, A. T. COWIE and ZENA D. HOSKING

SUMMARY

Five groups of five lactating rabbits each were used. Milk yield was recorded from the 8th day of lactation onwards and on the 10th day of lactation the rabbits received the following treatments: Group S, sham-operation with saline (1 ml/12 h); Group P, hypophysectomy with sheep prolactin (1 mg/12 h); Group H, hypophysectomy with human growth hormone (1 mg/12 h); Group B, hypophysectomy with bovine growth hormone (1 mg/12 h) and Group C, hypophysectomy with saline (1 ml/12 h). The injections of saline or hormones were continued for 5 days and at the end of this period a blood sample was taken, the animals were killed and their mammary glands removed for histological examination and assay of the following enzymes: 6-phosphogluconate dehydrogenase (EC 1.1.1.44), phosphofructokinase (EC 2.7.1.11), phosphoglucomutase (EC 2.7.5.1), UDP-glucose pyrophosphorylase (EC 2.7.7.9), acetyl-CoA carboxylase (EC 6.4.1.2), acetyl-CoA synthetase (EC 6.2.1.1) and ATP-citrate lyase (EC 4.1.3.8). On the 5th day after surgery the concentrations of blood l-lactate and pyruvate and plasma free fatty acids and protein were similar in all groups, whereas plasma glucose was higher in groups S, B and H than in groups P and C. Although the weights of pituitary target organs (adrenals, thyroid and ovaries) were similar in all groups, the weights (g/kg body weight) of mammary tissue varied markedly, group S being the heaviest and group C the lightest. Milk yields, 5 days after surgery, for groups P and H were about 50% that for S, whereas those for B and C were 15 and 4% respectively. Where possible the enzyme activity was expressed as a ratio of the rate of synthesis of the end product of the pathway in which the enzyme occurred. With the exception of acetyl-CoA carboxylase which may have had a rate-limiting role in the synthesis of milk fat, enzymic activity in vitro was in excess of that required in vivo for the synthesis of either milk fat or lactose. It appeared that the rate of milk synthesis depended upon the degree of maintenance of the secretory epithelial cells within the mammary gland rather than a block in the synthetic pathways within these cells.

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J. K. KULSKI, MARGARET SMITH and P. E. HARTMANN

Departments of Biochemistry and *Obstetrics and Gynaecology, University of Western Australia, Nedlands, Australia

(Received 25 April 1977)

The hormonal signal for lactogenesis in a number of different species is considered to be a precipitous fall in the concentration of progesterone in the blood during late pregnancy (see Hartmann, Trevethan & Shelton, 1973). In women, the major fall in the level of blood progesterone just after delivery (Yannone, McCurdy & Goldfien, 1968) precedes lactogenesis by 2-3 days (Reynolds, 1972). However, the effects of this fall may be modified to some extent by progesterone, which accumulates in the milk (Heap, Gwyn, Laing & Walters, 1973). Progesterone could be the 'lipid-soluble substance' in the mammary secretion which Linzell & Peaker (1974) suggested might control the final stage of lactogenesis. The purpose of the present investigation was to compare changes in the concentrations of progesterone, lactose and α-lactalbumin in the mammary secretion of women

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J. L. Whitely, P. E. Hartmann, D. L. Willcox, G. D. Bryant-Greenwood and F. C. Greenwood

ABSTRACT

The synthetic progestagen, medroxyprogesterone acetate (MPA), was administered to sows in late pregnancy with the objective of slightly delaying the time of farrowing and thereby providing more marked associations between hormonal changes and the termination of pregnancy, and the initiation of farrowing and lactation in this species.

MPA was administered orally (140 mg, twice daily) to eight sows in late pregnancy on days 112, 113 and 114 of gestation. Parturition was then induced to occur on day 116 by injecting 200 μg cloprostenol i.m. on day 115 of gestation. The peripartum changes in the plasma concentrations of progesterone, cortisol, oestradiol-17β, relaxin, prolactin, lactose and 13,14-dihydro-15-keto prostaglandin F (PGFM) were measured in these sows together with a group of untreated sows. The gestational length for the MPA-treated sows (116·3 ± 0·3 days, mean±s.e.m.) was significantly (P<0·01) greater compared with the untreated sows (114·9 ± 0·3 days). Plasma progesterone declined earlier (P<0·05) with respect to the time of parturition in the treated sows compared with the untreated group. With respect to the timing of parturition, the time at which maximal concentrations of relaxin were attained and the timing of the subsequent decline were earlier in the MPA-treated sows. In both groups of sows, the concentration of relaxin increased before the decline in plasma progesterone. In the untreated sows, the concentration of PGFM increased either slightly before or at the same time as the decline in plasma progesterone, whereas in sows treated with MPA, progesterone concentrations began to decline before any significant increase in the plasma concentration of PGFM. The profiles of cortisol, oestradiol-17β and PGFM were similar in both groups of sows. In both groups of sows, the timing of the initial increase in the concentration of plasma prolactin coincided with a similar rise in plasma lactose (P<0·01). Plasma progesterone either declined earlier or at the same time as the rise in plasma lactose (P<0·01) in the treated group of sows only.

We conclude that since the prepartum changes in the concentration of progesterone and relaxin occurred before significant changes in the concentration of PGFM in the MPA-treated sows, the nature of the luteolytic factor and the mechanism by which it exerts its action remains obscure. The higher concentration of lactose in the mammary secretion at birth in the MPA-treated sows compared with the untreated group suggested that lactogenesis was initiated earlier with respect to parturition following MPA treatment. Furthermore, the administration of MPA to sows in late pregnancy delayed the onset of parturition but did not inhibit lactogenesis.

Journal of Endocrinology (1990) 124, 475–484