J. Physiol. (1979), 288, pp. 33-44 With 5 text-figurem Printed in Great Britain

33

CHANGES IN MAMMARY FUNCTION AT THE ONSET OF LACTATION IN THE GOAT: CORRELATION WITH HORMONAL CHANGES*

BY A. J. DAVIS, I. R. FLEET, JANE A. GOODE, MAUREEN H. HAMON, FELICITY M. MAULE WALKER AND M. PEAKERt From the Agricultural Research Council Institute of Animal Physiology, Babraham, Cambridge CB2 4AT SUMMARY

1. Changes in mammary function and plasma hormone concentrations during late pregnancy and the onset of lactation have been studied in conscious goats. 2. Mammary blood flow, oxygen consumption and glucose uptake increased markedly and significantly between 2 days and 05-1 day pre-partum. 3. The increase in mammary glucose uptake was relatively greater than that of oxygen consumption or blood flow. 4. The concentration of citrate in mammary secretion increased; the first significant change was apparent 05-1 day pre-partum but the main rise occurred after this time. 5. It is concluded that the marked increase in mammary glucose uptake 05-1 day before parturition indicates the time of onset of copious milk secretion. 6. The first significant increase in the concentration of unconjugated oestrogens in arterial plasma occurred 3 days pre-partum, whereas the first significant decrease in progesterone and increase in 13,14-dihydro-15-oxoprostaglandin F2X occurred 051 day pre-partum, thus coinciding with the mammary changes; there was also a peak in prolactin concentrations at the latter time. 7. The hormonal changes are-discussed in relation to current concepts of the initiation of parturition and the onset of copious milk secretion in this species. It is suggested that the fall in plasma progesterone concentrations triggers milk secretion at high rates. INTRODUCTION

The changes that occur in the mammary gland at the onset of copious milk secretion associated with birth of the young have been little studied. Many investigators have compared some aspect of mammary function in the pregnant and lactating states but very few (Kjaersgaard, 1968; Reynolds, 1969; Linzell, 1974; Burd, Lemons, Makowski, Battaglia & Meschia, 1975) have studied the time course and magnitude of the changes in physiological terms especially as related to milk secretion. In the goat, Fleet, Goode, Hamon, Laurie, Linzell & Peaker (1975) divided lactogenesis into two stages: lactogenesis stage I is the onset of secretary activity, i.e. the gradual appearance of pre-colostrum in the gland, which occurs some weeks *

Reprint requests to F. M. M. W.

t Present address: The Hannah Research Institute, Ayr, Scotland KA6 5HL. 2

PHY

288

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34

A. J. DA VIS AND OTHERS

pre-partum, while lactogenesis stage II is the onset of copious milk secretion at about the time of parturition. In the present paper changes in mammary function have been studied during lactogenesis stage II in conscious goats. Although there have been numerous endocrinological studies in the goat during late pregnancy and at parturition (the most recent hypothesis is outlined in Table 2), it is difficult to compare mammary and hormonal changes in different animals. Therefore, in our studies, changes in circulating hormone concentrations have been investigated in the same animals in order to try to determine the physiological endocrine trigger to copious milk secretion. Progress on this topic has been hampered by lack of knowledge of the precise timing of lactogenesis (see Kuhn, 1977); this is because it is difficult to determine the rate of secretion of milk and milk components or the uptake of milk precursors. For example, it is not possible to determine the normal rate of milk secretion by milking pre-partum since the act of milking can

influence the yield and composition by a local mechanism (see Linzell & Peaker, 1974); in addition in small animals the amount of fluid that can be removed may bear little relation to the rate of secretion. Studies based on the concentration of milk constituents in mammary tissue or secretion are difficult to interpret because different milk components appear at different times and the data, with few exceptions, give little information on the rate of secretion. Changes in mammary volume are also compounded by alterations in tissue volume as well as by the accumulation of secretion. The alternative approach of measuring the uptake of milk precursors by the gland is difficult in most animals. However, in the present study it has been possible to define the time of onset of copious milk secretion by measuring precursor uptake in conscious goats and to correlate the marked changes with hormonal events. Using this correlative approach, hypotheses are outlined which can later be subjected to experimental testing in this species. METHODS

The experiments were conducted on six trained Saanen, or predominantly Saanen Animao. goats, surgically prepared for the collection of mammary venous and arterial blood, cross-bred in which vessels between the two mammary glands were ligated and in which a 'milk' (caudal

superficial epigastric) vein and a carotid artery were exteriorized in loops of skin (Linzell, 1960, 1963). At the start of the experiments the goats were in their 2nd to 9th pregnancy, and the previous lactation had ceased at least 10 weeks previously. All were allowed to proceed normally to term, and the gestation periods were from 144 to 152 days (in this herd 90 % of deliveries occur between 146 and 154 days - median 150 days - Peaker, 1978a). All young (1, 2, 2, 3, 3, 4 in the six goats) were delivered alive. Protocol. Measurements were usually made between 10.00 and 12.00 hr except near parturition when determinations were made more frequently. On each occasion, mammary blood flow was determined by Linzell's (1966a) thermodilution technique. Carotid arterial (7 ml.) and mammary venous (10 ml.) samples were taken at the same time through fine needles, the former under local (lignocaine) anaesthesia; coagulation was prevented by the addition of a small drop of heparin solution (5000 u./ml.). Blood flow was measured, and venous samples taken, while the animal was standing and while the external pudic vein at the base of the udder was being compressed manually; this was done to obtain true mammary venous blood (Linzell, 1960). After analysis of blood for gases, pH and packed cell volume (P.c.v.), the rest of the sample was centrifuged at 40C and the plasma divided into several lots for storage at -20 0C or - 10 0C before hormone and chemical analyses respectively. However, samples for prostaglandin assay were centrifuged immediately and plasma transferred to siliconized vials

LACTOGENESIS IN THE GOAT

35

for storage. Mammary uptake or output of substances was calculated as the product of blood flow and arteriovenous (A-V) difference in blood concentration, or as plasma flow (blood flow corrected by r.c.v.) and A-V difference in plasma concentration. Prior to parturition, samples of mammary secretion (5-10 ml.) were taken aseptically from each teat by gentle hand-milking; the teat was then sealed with pliable plastic film (Nobecutane spray, B.D.H.). After parturition, samples were taken at the time of milking. The young were removed for hand-rearing several hours after birth. Accumulated colostrum was then milked out, and after two I.v. injections of 100 m-u. oxytocin, empty udder volume was determined (results not reported in this paper). Thereafter the goats were milked twice daily at approximately 09.00 and 16.30 hr; the yields of the two glands and the time of milking were recorded. This procedure was adopted to obtain a true measure of changing milk yield as soon as possible after parturition. It should be borne in mind that a balance had to be struck between the necessity for frequent measurements and the ability of the vein loop to withstand continual puncturing for the measurement of blood flow. Chemical analy8e8. Mammary secretion was analysed for citrate (White & Davies, 1963), phosphate (Technicon method N-4c for dialysable inorganic phosphate), lactose, Na, K, Cl (Fleet, Linzell & Peaker, 1972) and for total calcium (atomic absorption spectrophotometry). Blood gases and r.cv. were determined as described by Linzell & Peaker (1975). Plasma samples were analysed for glucose (glucose oxidase-perid method, Boehringer Mannheim, in a Technicon autoanalyzer) and some for acetate (Lindsay & Setchell, 1976). Hormone analyses by radioimmunoamsay. Plasma samples were analysed for progesterone (Heap, Gwyn, Laing & Walters, 1973), total unconjugated oestrogens (Challis, Heap & Illingworth, 1971), oestradiol-17,f (Challis et al. 1971), prolactin (Wright, Jenkin, Heap & Walters, 1978) and 13,14-dihydro-15-oxoprostaglandin F2a, also known as 13,14-dihydro-15-ketoprostaglandin F2a and abbreviated to DHK-PGF2, (see below). It is generally considered that placental lactogen does not cross-react in prolactin radioimmunoassays (Buttle, Forsyth & Knaggs, 1972). In the total unconjugated oestrogen assay, cross-reactivities at 50 % binding (as percentages) (R. B. Heap & E. L. Sheldrick, unpublished) were: oestrone 100, oestradiol-17fl 110, oestradiol-17a 8, other estrogens and progesterone < 1, and in the oestradiol-17fl assay: oestradiol-17,f 100, other oestrogens and progesterone < 1. For DHK-PGF2,, three volumes (50-500 #1.) of each plasma sample were taken to pH 3-0 with one tenth volume 7-29 M-citric acid. Following the extraction of prostaglandins in 2 x 3 ml. peroxide-free diethyl ether and drying, the extracts were dissolved in 1 ml. 100 mm-Tricine buffer at pH 8-0. Samples (100 4ed.) were then assayed in duplicate by the method of Mitchell, Flint & Turnbull (1976). Efficiency of extraction was determined from the recovery of [3H]DHKPGF2a (75 c/m-mole; Radiochemical Centre, Amersham) added to plasma samples (90-2 + 6-9 S.D. %). Cross-reactivities were similar to those described by Mitchell et al. (1976). Recoveries of unlabelled DHK-PGF2,, were 0-48 + 0-03 (mean + S.D. in seven assays) for 0-5 ng/ml. to ovariectomized goat plasma, 0-95 ± 0-08 for 1 ng/ml. and 2-42 + 0- 10 for 2-5 ng/ml. RESULTS

In this paper, the mean data (+ s.E.) for the six goats are presented bulked in time over fixed periods before and after parturition (shown by horizontal bars in the Figs.), and mammary metabolic values as a percentage of the value obtaining in each animal on days 7-9 pre-partum; in each case statistical significance was tested by a paired t-test and before transformation into percentages. However, it should be borne in mind that the presentation of mean data may mask some of the more subtle changes occurring in individual animals. Values obtaining on days 7-9 pre-partum, the starting time for all variables studied, are shown in Table 1. The presentation of results of this nature is complicated by such factors as the lack of standard sampling times with respect to the time of parturition and the varying time courses of some of the changes in different individuals. Furthermore, the size 2-2

A. J. DAVIS AND OTHERS 36 of the mammary glands varies widely between individual goats, and the glands contain varying amounts of accumulated secretion in late pregnancy. The fluid cannot be removed by milking at this stage without causing changes in the composition and rate of secretion (Linzell & Peaker, 1974 and unpublished results). Therefore, an estimate of the volume of mammary tissue cannot be obtained, and mammary metabolic variables cannot be expressed per unit weight of tissue. TABLE 1. Initial values for determinations of mammary function and plasma hormone and glucose concentrations made 7-9 days pre-partum in six goats. Also shown is the milk yield on day 6 po8t-partum Mean s.E. Range Both glands Udder volume* (1.) 4-2+0-53 12.1-5-4 Gland studiedt Blood flow (ml./min) 211+22.6 176-321 8.4-17.7 Oxygen uptake (ml./min) 13.7 + 1.44 Glucose uptake (mg/min) 8.5 + 1 72 2.6-15-2 6.2 + 0 50 4.6-7-7 Oxygen A-V difference (ml./100 ml. blood) 4-5-6-5 Glucose A-V difference (mg/100 ml. plasma) 5.5 + 0-39 6-46 Secretion citrate concentration 20 + 6-7

Arterial plasma Glucose (mg/1OO ml.) Progesterone (ng/ml.) Prolactin (ng/ml.)t Oestrogens (ng/ml.)t DHK-PGF2, (ng/ml.) Milk yield of both glands on day 6 post-partum (1./day) *

46+5-8 3 97 + 0-36 132 + 20.0 0-774+ 0-143 0-889+ 0'178 3-02 + 0-31

41-57 2.5-5.2 85-221 0-409-1-356 0.390-1-600

2-17-3-96

Including accumulated fluid.

t One gland in each animal prepared with milk vein loop. t Prolactin expressed as ovine prolactin NIH P-S-10 ng/ml., total unconjugated oestrogens as

oestradiol-17fl ng/ml.

Mammary blood flow, metabolism and milk secretion Mammary blood flow, oxygen consumption and glucose uptake all increased markedly near term, the first statistically significant change with respect to days 7-9 being evident at 0-5-1 day pre-partum, although these variables had shown some tendency to increase slightly over the preceding week (Fig. 1). Mammary blood flow and oxygen consumption reached a peak on day 1-1-5 post-partum and declined somewhat thereafter; a similar pattern is evident in the data of Reynolds (1969). The relative increase in glucose uptake was greater than the increase in blood flow, whereas the relative increase in oxygen consumption was similar to that of blood flow. Thus on days 4-6 post-partum, mean glucose uptake was 920 %, oxygen uptake 192 % and blood flow 195 % of the values on days 7-9 pre-partum. This difference was due to increases in the A-V differences for glucose but not for oxygen; the first statistically significant increase in glucose A-V difference was evident at 0-5-1 day pre-partum (Fig. 1). In other words, the increased uptake of glucose can be attributed to an increase in both mammary blood flow and A-V difference while the increase in oxygen consumption was related to the increase in blood flow alone. When individual values for glucose uptake (Yl) or oxygen uptake (Y2) are considered

37 LACTOGENESIS IN THE GOAT in relation to blood flow (x) the calculated regression line for oxygen uptake vs. blood flow (Y2 = 44+0 7x, r = 0*753, P < 0*001) falls close to the 450 (slope = 1) line, whereas that for glucose uptake vs. blood flow (Yi = 20+ 27x, r = 0-604, P < 0.001) lies well above the 450 line. The slopes 0 7 and 2-7 are significantly different (P < 0.001). In three goats, acetate uptake was also studied when there was sufficient plasma

30011 3,IU)

200 E

'U o-% .2

8a'

100

-

0o1-0 200 [ 300 a,

02 uptake C02 Output (% previous)

100 86-

>-- -o

0

o .Q w 0

0 I

100 800 600

I0'

*0-

200 _

-

-

-

- 8\

o Cv

400aE~ 200 0.2016 -O E 12 8 _

*i
40 _+ 0

+i+ ,

*

-987 6 5 4 3 2 1 0 1 2 3 4 5 +6 Time (days) from parturition

Fig. 3. Changes in the citrate concentration of the mammary secretion in six goats, plotted as in Fig. 1. Mean + s.E.

There were also changes in the glucose concentration of arterial plasma. A significant mean increase of 50 % at 0-5-1 day pre-partum was apparent; thereafter the mean concentration fell and by 2-3 days postpartum was significantly lower, by 20 %, than the value on days 7-9 pre-partum (Fig. 1). Secretion composition As found previously (Peaker & Linzell, 1975; Fleet et al. 1975), the concentration of citrate in the secretion increased markedly at about the time of parturition. In the present experiments, the first significant change was at 0 5-1 day pre-partum

(Fig. 3).

The concentrations of sodium and chloride decreased while those of potassium and lactose increased during late pregnancy, as previously described (Linzell & Peaker, 1974; Fleet et al. 1975); there were no significant changes in total calcium or dialysable inorganic phosphate.

Hormones in arterial playu The first significant change observed was a rise in the concentration of total unconjugated oestrogens 3 days pre-partum. The rise continued until term after which there was a precipitous fall to barely detectable levels (Fig. 4A). The marked

LACTOGENESIS IN THE GOAT 39 variation in the value for O0-*5 days postpartum is related to the bulking of values over this period, those close to parturition being high, those taken later being low. In three animals, oestradiol-17fl concentrations were also determined. In general, the pattern of change was similar to that for total unconjugated oestrogens except that concentrations reached a peak 2 days pre-partum and fell thereafter (Fig. 4B). Although the progesterone concentration showed a tendency to fall slightly between 7-9 days and 2 days pre-partum, the first significant and marked fall was apparent 05-1 day pre-partum. The fall continued, with progesterone reaching very low concentrations by term (Fig. 4A). A 4-

3E

2 Ent~2 35 C -

0

:

-

200

-6

1 00

2.0[

p.C.

1.6 -

0= -E 1.2 a,' 0.8

_

0 8

I E

2

2 B

~.160.~.120-

o 400 -9 7 5 3 1 1 3 5 8 6 4 2 0 2 4 +6 Time (days) from parturition

Fig. 4. Arterial plasma concentrations, plotted as in Fig. 1. A, progesterone, prolactin (expressed as equivalent concentration of ovine prolactin NIH P-S-10), oestrogens (total unconjugated, expressed as equivalent concentration of oestradiol-17fi) and DHK-PGF2,. Mean+ S.E. in six goats. B, oestradiol-17,f. Mean in three goats.

Prolactin concentrations were relatively high during the entire period studied but a peak was evident at 05-1 day pre-partum (Fig. 4A). The possibility that the stress of sampling caused an increase in prolactin release must be considered, but the

A. J. DAVIS AND OTHERS 40 values obtained within goats were consistent and the animals were accustomed to the procedure. Prolactin determined in samples taken several hours after morning milking in the postpartum period do not necessarily indicate biologically significant values since Hart (1973) found peaks of high concentration to occur immediately after milking. Since DHK-PGF2. is the major primary metabolite of PGF2. appearing in the peripheral circulation (Samuelsson, Granstrdm, Green & Hamberg, 1971), the concentration of this compound in arterial plasma reflects the total production of PGF2.; in sheep, for example, changes in DHK-PGF2, have been shown to parallel changes in uterine PGF2. output (Mitchell et al. 1976). Like the fall in progesterone and the peak in prolactin, the first apparent change in the peripheral (arterial) concentration of DHK-PGF2, was a marked rise at 0.5-1 day pre-partum. Maximum values were attained near term, after which the concentration fell. DISCUSSION

The results show that the mammary uptake of glucose, oxygen and acetate, and mammary blood flow, increase before term, with a dramatic rise starting, as accurately as can be judged from these experiments, between 2 days and 0.5-1 day prepartum. Since glucose is required for lactose synthesis (see Linzell, 1974), since lactose is required for water secretion (see Linzell & Peaker, 1971; Peaker, 1978b) and since milk is approximately 90 % water, then clearly the marked increase in the uptake of glucose indicates the onset of copious milk secretion or lactogenesis stage II. The increase in glucose uptake was related to an increase in the A-v difference as well as to an increase in blood flow. Therefore, the extraction (A-v difference/arterial concentration) of glucose from the blood by the secretary cells must have increased since, with a constant extraction and a rising blood flow, the A-v difference would have been expected to fall. In lactation there are strong indications that in normal physiological circumstances mammary blood flow is controlled by vasodilator substances produced by the active gland, and blood flow and milk yield are positively correlated (see Linzell, 1974). Fleet & Peaker (1978) found that following the cessation of milking in the goat, blood flow was more closely related to oxygen uptake and, therefore, to metabolic or oxidative activity than to glucose uptake or the rate of milk secretion. Similarly, in the present work, blood flow was more closely correlated with oxygen consumption than with glucose uptake. There was a tendency for mammary blood flow, oxygen consumption and glucose uptake to increase slowly between 7-9 and 2 days pre-partum. Whether these apparent trends were related to slowly changing hormonal concentrations is difficult to assess since they could as easily be related to the growth of the tissue which occurs at this time (Linzell, 1966b; Fleet et al. 1975). As found previously, the concentration of citrate in the secretion is a good indicator of the onset of copious secretion (Peaker & Linzell, 1975; Fleet et al. 1975). However, although the first significant change was apparent at the same time as that of glucose uptake, the main rise occurred later (Fig. 5), as would be expected since citrate in milk is derived from blood glucose and acetate (Hardwick, Linzell

LACTOGENESIS IN THE GOAT

41

1000 4

0@

800

_ +

*--4 m

3 c U

E ' > 600

o

2 "N ' 400 Gn

1

° m

200 (m 0.C

C

.0

300

E X

m

200p-

-A

L.

a

E _-.

100_ c

E

0VI X0

140

-

100

E

60

-

0 _-9 8 7 6 5 4 3 2 1 0 1 2 3 4 5+6 Time (days) from parturition

Fig. 5. Mammary glucose uptake, arterial plasma progesterone and prolactin concentrations, and secretion citrate concentration in six goats. Mean data from Figs. 1, 3 and 4. The open circles indicate the first occasion a value was significantly different from that obtained at 7-9 days pre-partum.

TABiLE 2. Relations between the sequence of events which have been proposed to lead to the onset of labour in goats, the changes in plasma hormone concentrations in the present experiments and the onset of copious milk secretion. Arrows indicate causal factors that have been decrease or are being proposed. T increase; Suggested sequence of events leading to parturition (Flint et al. 1978) Fetal signal

T T T

Changes in maternal plasma hormone concentrations in present experiments

Other hormonal changes in present experiments

Mammary changes

Cortisol in fetal circulation

Placental oestrogen

Uterine

production

T

Oestrogens

PGF2a production

T DHK-PGF2.2

Luteolysis Progesterone secretion

J

and | Progesterone

.Prolactin

Onset of copious milk

secretion

Further uterine

PGF2,

production Further T

Onset of labour

DHK-PGF2.

42 A. J. DA VIS AND OTHERS & Mepham, 1963; Smith & Taylor, 1977). Therefore, it appears that lactogenesis stage II begins a little earlier than the main rise in citrate concentration. In trying to correlate the hormonal and mammary events leading to lactogenesis stage II, we shall confine the discussion to the goat since the hormonal control of pregnancy and parturition differs widely between species (Heap, Galil, Harrison, Jenkin & Perry, 1977). There have been a number of studies of the endocrine events leading to parturition in the goat (see, for example, and references in Buttle et al. 1972; Hart, 1972; Currie & Thorburn, 1977; Flint, Kingston, Robinson & Thorburn, 1978). The present results are consistent with those reported for peripheral plasma. The time course of the hormonal changes is compatible with the current hypothesis on the induction of parturition in the goat (Flint et al. 1978) as shown in Table 2. Kuhn (1977) has reviewed the comparative aspects of the hormonal initiation of copious milk secretion in terms of three concepts. (i) The mammary cells are inhibited from responding to the prevailing concentrations of prolactational hormones (e.g. prolactin, placental lactogen, adrenocorticosteroids) in late pregnancy by progesterone, and that it is the fall in progesterone which triggers copious secretion. (ii) The concentrations of prolactational hormones rise to breach the threshold of inhibition by progesterone. (iii) Both processes occur so that no precedence can be ascribed to either. He tentatively concluded that evidence is favouring the first mechanism, and it seems to us that this is most likely to apply in the goat since not only does the timing of lactogenesis stage II coincide with the marked fall in progesterone prepartum (Fig. 5) but the gland is exposed to a prolactational environment throughout middle and late pregnancy caused by placental lactogen and prolactin (see Forsyth & Hayden, 1977) and, even though there is a peak in prolactin concentrations, as Kuhn (1977) argues, there may actually be no net increase in the concentrations of prolactin-like material at the time of lactogenesis. Such a view is strengthened by recent studies on prolactin-like activity in the plasma of goats throughout pregnancy using a radioreceptor assay (Currie, Kelly, Friesen & Thorburn, 1977). These correlative studies in the goat therefore indicate not only a close linkage between the events leading to parturition and those leading to the onset of copious milk secretion but that the pre-partum fall in plasma progesterone concentrations is likely to provide the mammary stimulus to high rates of secretary activity. We are most grateful to Dr B. J. A. Furr, I.C.I. Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire, Dr J. R. McNeilly and the Upjohn Company, Kalamazoo, U.S.A. for the gift of antisera. We are also grateful to Dr R. B. Heap and Dr A. P. F. Flint for advice on endocrine matters, and to Mr R. Proudfoot and Mr A. Bucke for their diligent care of the animals.

LACTOGENESIS IN THE GOAT

43

REFERENCES

BURD, L. I., LEmoNs, J. A., MAowsxi, E. L., BA¶IrAGLIA, F. C. & MEsRcA, G. (1975). Relationship of mammary blood flow to parturition in the ewe. Am. J. Phy8iol. 229, 797-800. BuLE, H. L., FORSYTH, 1. A. & KNAGGS, G. S. (1972). Plasma prolactin measured by radioimnmunoassay and bioassay in pregnant and lactating goats and the occurrence of a placental lactogen. J. Endocr. 53, 483-491. ALISS, J. R. G., HEAP, R. B. & ILLINGWORTE, D. V. (1971). Concentrations of oestrogen and progesterone in the plasma of non-pregnant, pregnant and lactating guinea-pigs. J. Endocr. 51, 333-345. CuImm, W. B., KELLY, P. A., FRrEsms, H. G. & THORBTuRN, G. D. (1977). Caprine placental lactogen: levels of prolactin-like and growth hormone-like activities in the circulation of pregnant goats determined by radioreceptor assays. J. Endocr. 73, 215-226. CutRRIE, W. B. & THORBURN, G. D. (1977). The fetal role in timing the initiation of parturition in the goat. In The Fetw and Birth, Ciba Foundation Symposium 47, 49-66. Amsterdam:

Elsevier/Excerpta Medica/North-Holland. FLEET, I. R., GOODE, J. A., HAMON, M. H., LAURIE, M. S., LrNzErm, J. L. & PEAKER, M. (1975). Secretory activity of goat mammary glands during pregnancy and the onset of lactation. J. Physiol. 251, 763-773. FLEET, I. R., LmrzErnL, J. L. & PEAKER, M. (1972). The use of an autoanalyzer for the rapid analysis of milk constituents affected by subclinical mastitis. Br. vet. J. 128, 297-300. FLEET, I. R. & PEAKER, M. (1978). Mammary function and its control at the cessation of lactation in the goat. J. Physiol. 279, 491-507. FLINT, A. P. F., KINGSTON, E. J., ROBINSON, J. S. & THORBUEN, G. D. (1978). The initiation of parturition in the goat: evidence for control by foetal glucocorticoid through activation of placental c2, steroid l70c-hydroxylase. J. Endocr. 78, 367-378. Fousym, I. A. & HAYDEN, T. J. (1977). Comparative endocrinology of mammary growth and lactation. In Comparative Aspects of Lactation, ed. PEAKER, M. Symp. zool. Soc. Lond. 44, pp. 135-163. London: Academic. HARDWICK, D. C., LINZELL, J. L. & MEPHAM, T. B. (1963). The metabolism of acetate and glucose by the isolated perfused udder. 2. The contribution of acetate and glucose to carbon dioxide and milk constituents. Biochem. J. 88, 213-220. HART, I. C. (1972). A solid phase radioimmunoassay for ovine and caprine prolactin using sepharose 6B: its application to the measurement of circulating levels of prolactin before and during parturition in the goat. J. Endocr. 55, 51-62. HART, I. C. (1973). Basal levels of prolactin in goat blood measured throughout a 24-h period by a rapid double antibody-solid phase radioimmunoassay. J. Dairy Res. 40, 235-245. HEAP, R. B., GALIL, A. K. A., HARRISoN, F. A., JENKIN, G. & PERRY, J. S. (1977). Progesterone and oestrogen in pregnancy and parturition: comparative aspects and hierarchical control. In The Fetus and Birth, Ciba Foundation Symposium 47, 127-150. Amsterdam:

Elsevier/Excerpta Medica/North-Holland. HEAP, R. B., GwYv, M., LAING, J. A. & WALTERS, D. E. (1973). Pregnancy diagnosis in cows: changes in milk progesterone concentration during the oestrous cycle and pregnancy measured by a rapid radioimmunoassay. J. agric. Sci., Camb. 81, 151-157. KJAERsGAARD, P. (1968). Mammary blood flow ante and post partum in cows. Acta vet. scand. 9, 180-181. KuEN, N. J. (1977). Lactogenesis: the search for trigger mechanisms in different species. In Comparative Aspects of Lactation, ed. PEAKER, M. Symp. zool. Soc. Lond. 41, pp. 165- 192. London: Academic. LINDSAY, D. B. & SETCEELL, B. P. (1976). The oxidation of glucose, ketone bodies and acetate by the brain or normal and ketonaemic sheep. J. Physiol. 259, 801- 823. LINZELL, J. L. (1960). Mammary-gland blood flow and oxygen, glucose and volatile fatty acid uptake in the conscious goat. J. Physiol. 153, 492-509. LrNZELL, J. L. (1963). Carotid loops. Am. J. vet. Re8. 24, 223-224. LINZELL, J. L. (1966a). Measurement of venous flow by continuous thermodilution and its application to measurement of mammary blood flow in the goat. Circulation Res. 18, 745-754. LrNzELL, J. L. (1966b). Measurement of udder volume in live goats as an index of mammary growth and function. J. Dairy Sci. 49, 307-311.

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Changes in mammary function at the onset of lactation in the goat: correlation with hormonal changes.

J. Physiol. (1979), 288, pp. 33-44 With 5 text-figurem Printed in Great Britain 33 CHANGES IN MAMMARY FUNCTION AT THE ONSET OF LACTATION IN THE GOAT...
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