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Endocrine Activity of the Mammary Gland: Oestrogen and Prostaglandin Secretion by the Cow and Sheep Mammary Glands During Lactogenesis
Br. vet. }. (1983) . 139, 171
ENDOCRINE ACTIVITY OF THE MAMMARY GLAND: OESTROGEN AND PROSTAGLANDIN SECRETION BY THE COW AND SHEEP MAMMARY GLANDS DURING LACTOGENESIS
BY F. M . MAULE WALK ER,
A. j . DAVI S AND I. R.
FLEET
Agricultural Research Council Institute of Animal Physiology, Babraham, Cambridge CB2 4A T .
SU MMARY
M a mm ary venous and ca rotid arterial plas m a concentrations of oestradiol-17{3 a nd prostagla ndin Fa (PGF a), a nd mammary secre tion co ncentrations of lactose were d ete rmin ed in three j ersey cows and four Friesland sheep from seven d ays pre-partum until two days post partwn. Sign ifi ca nt mammary secretion of oes tradiol-17{3 a nd PGFa into th e venous drainage was observed in both cows a nd sheep pre-partum, supporting the hypo th es is postul a ted for th e goat that th e m a mm ary g la nd is a n e ndocrin e organ . The timing of th e onset of co pious milk secre ti on, co in cid ent with a n increased m a mm a ry secretion co ncentration of lactose (lactogenesis), differed between cows a nd sheep in relation to parturition. H oweve r, th e tempora l pa ttern of cha nges in the mamm a r y secret ion of oes tradiol-17{3 a nd PGFa, in relation to lactoge nesis, was simil ar in th e two spec ies; a cessa ti on of m a mm a ry secretion of PGFa a nd a transient peak in th e ma mm a ry secretion of oestradiol-17{3 occurrin g imm edi ate ly pri or to th e onset of cop io us milk secretion . This relationship is similar to that o bserved prev iou sly in the goa t, a nd indi cates co mm on mechanisms fo r the co ntrol of lactoge nesis in these three ruminants which h ave differing e nd ocrinol ogical profiles associated with th e m a inte na nce of pregnancy a nd co ntrol of pa rturiti on .
I NTRODUCT I ON
Earlier st udi es in goats (Mau le W al ke r & Pcaker, 1978, 1980 ) d e mons tra ted substa nti a l mammary secre ti on of oes trad iol- 17{3 a nd produ cti on of prostaglandin Fa (PGFa) during la te preg na ncy. The secret io n of PGFa a nd oest radiol-17{3 into the mammary venous pla sma in creased to peak va lu es pre-partum a nd subseq uently decl in ed to undetectab le leve ls cl ose to parturition, in assoc ia ti on with the onset of co piou s milk secretion. Inhibiti o n of ma mm ary prod uction of prostagla ndin s disrupts the co urse of lactogenes is in this spec ies, but ca n be overcome to so m e ex tent by the
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BRITISH VETERINARY .JOURNAL, 139, 2
administration of exogenous oestrogen (Maule Walker, 1982) . The present study was undert a ken in two other dairy ruminants, the Jersey cow and th e Friesland sheep, which show a different temporal pattern in the relationship between lactogenes is a nd parturition compared with the goat. The aim was to establish whether the mammary glands of these rumin a nts show endocrine activities simi lar to those observed in th e goat in relation to the onset of copious milk secretion .
MATERIALS AND i'viETHODS
Three jersey cows and four Friesland sheep were surgically prepared for the collection of arterial and mammary venous blood by the methods d escribed by Linzell ( 1960) for goats with a carotid artery and a 'milk' (caudal superficial epigastric) vein exteriorized in skin-covered loops. At the start of these studies th e cows were in their fourth to seventh pregnancies and the sheep were in their second to fifth pregnancies; the exact stage of gestation was known for a ll animals. Milking had ceased approximately 14 weeks (cows) or 10 weeks (sheep) prior to parturition. P a rturition occurred in the cows between 281 and 284 days gestation, and in the sheep between 144· a nd 14·7 clays gestation. All young were born alive and survived to wea ning . The young were removed as soon as possible a nd routine twice-daily milking begun . The period studied was from seven d ays pre-parium until two d ays post parlwn . Pa ired carotid arterial a nd mammary venous blood samples we re ta ken between I 0.30 a nd 11 .30 h daily . The sheep were sampled slightly more frequently than the cows, a n additional sample be ing obtained approximately 12 h pre-partum. Coagulation of bl ood samples was prevented by the addition of heparin (10 to 15 units/ m l blood) . Mammary b lood samples were collected and mammary blood flow was determin ed by continuous thermodilution (Linzell, 1960, 1966 ; Linzell & R as mussen, 1972) while the animal was standing and the external pudic vein at the base of th e udder was compressed manu a lly ; this was done to obtain tru e mammary venous blood (Linzell, 1960 ; Linzell & R as musse n, 1972) . In some of th e s hee p th ere was a small mid-lin e superficial epigastric vein in addition to th e ' milk' vein exteriorized in a skin loop. In th ese an imals this mid -lin e ve in was a lso m a nually compressed. After re mova l of a small sample for the det ermination o f pac ked cell volume (PCV ), blood was immedi a te ly centrifuged a t 4°C and the pl as m a stored at -20°C until a nalysed. Prior to parturition small (I to 2 ml) samples of mammary secretion we re ta ken by hand milking ase ptically . Larger volumes of mammary secretion were no t taken jJre-parlum since thi s ca n indu ce premature lac togenes is in sheep (Maule W a lk e r , Stewart & Thompson, 1982) a nd cows (sec Roo k & Wh ee loc k, 1967) . Pos t- pa rtum samp les of milk were ta ke n from pooled mid-milk obta in ed at rou tin e milkin g. Pl as m a samp les were a nalysed for prost ag la ndin F, (Maule W a lk e r & Pca kcr, 1980) an d oes tradio l-17{3 (C ha lli s, He a p & Illin gwo rth , 1971 ). Samples of m a mm a ry sec re ti o n were a nalysed for lac tose by th e m et hod of Fl ee t, Lin zc ll & Pea kcr ( 1972). Student's /-t es t was used to tes t th e statistical s ig nifi ca nce of paired data .
RE SU lTS
The carotid a rt eria l and mammary ven o us plasma co nce ntra tion s of PCf" and
ENDOCRINE ACTIVITY OF THE MAMMARY GLAND
173
oestradiol-17/3 from seven days pre-partum to two days post parium for the cows and sheep a re presented in Figs I a nd 2, respectively . PCJ~
In both the cows and sheep the mammary venous plasma concentration of PGF<> was significantly greater (P into the venous drainage by the cow and sheep mammary g lands was 173 ± 19 and 42 ± I ng/min, respectively . In the cows, mammary output ofPGFa into the venous plasma ceased a t three days pre-partum and remained absent over the remainder of the period studied. The concentration of PGF<> in the carotid arterial plasma increased from three to one days pre-partum, falling thereafter. In the sheep, the mammary venous plasma concentration of PGF<> remained signifi cantly (P
wo Plasma proslaglandin Fa
pg/ml
300
200
100
CA 0 Plasma oestradiol · 171l pgiml
~00
J
300
200 MV
l/ 100
, j,-
v }/
\
\
''L_~ \ I I
'\ I
0 Time from parturition days
Fig . \ . The con ce ntra tion of prosta glandin F0 and oes tradiol- 17{3 in mammary venous (l'v!V ) an d carot id a rt eria l (C i\ ) plasma in three j ersey cows from seven days pre-parium until two days poslfwrlwn. V a lu es arc mean :t SEM . MV p lasma ·· • •• • ··, Ci\ pla sma - -• - -• - -.
174
BRITISH VETERINARY JOURNAL, 139,2 n:t.
1100 Plasma prostaglandin pg/ml
Fa 10°0
y1
900 500
1.00
I
I
300
200
t~~~-rA
I
100
Plasma oestradiol -17 iJ pg/ml
90
,j,
80
I I
70
I I I I
60
I I I
50
LO
I I
I
)
30
I I
20
~
;¥
1 -6
5
3
2
0
2
3.
Time fro m parturition days
Fig . 2. The concen trations of prostag landin F0 a nd ocstrad iol-1 7{3 in mammary ve nous (M V) and caro tid a rt er ia l (CA) plasma in four Friesland sheep from six days Jm-partum until two day s fJos/ par/tan . Valu es a rc means :!: SEM . MY plas ma -- • -- • -- , CA plasma - -• - -• - -
Oestradiol- I 7{3 The m a mm a ry venous co nce ntra tion of oestrad iol-! 7{3 in both th e cows a nd shee p was sign ifi cantly (P<0-0 l ) greater than that of th e carot id a rt eria l p las m a fro m seve n d ays until four days pre-partum . After adju s tm ent for mea n mammary plasma fl ow during thi s time , m a mm ary output of PGFa into th e veno us p las ma of th e cows and sheep was 167 ± 44 a nd l-3 ± 0·4 ng/ min , respect ively. In th e cows th e mammary ou tput of oest rad iol-17{3 in to th e venous p lasma in creased sig nifi ca ntly (P < 0-001) a t three days pre-pa rtum to 530 ± 130 ng/min, decreasing dramatically thereafter, the output at term bein g 56± 18 ng/mi n . I n the shee p , m a mm ary venou s p lasma co nce ntra ti ons of oes tradio l- 17{3 were not sig nifi ca ntl y different from those of carotid a rt eri a l pl as m a from three to two days prepartum . Howeve r a peak in th e m a mm a ry output of oes tra di o l-17{3 into the venous
ENDOCRI N E ACTIVITY OF TH E M AMM ARY G LAN D
175
dra in age occurred one day pre-partum, th e m ea n va lue being 9·4 ± 0·8 ng/ min . At thi s tim e th e ca ro tid a rteri a l plasm a con centra ti o n in creased , was ma inta in ed unt il 0· 5 d ay pre-partum, a nd fell th erea fter . M a mm a ry output of oes tradi ol-17{3 into th e veno us dra in age ceased at 0·5 d ay pre-partum a nd re m a in ed a bsent over th e res t of th e tim e studi ed.
J\1ammmy secretion lactose concentrations In the cows the la ctose co nce ntra ti o n 111 th e ma mm a ry sec re ti o ns in crea sed g radu a ll y from 64 ± 12 to 71 ± 5 m M ove r th e peri od of seven to four d ays pre-partum . At three d a ys pre-partum th e co nce n tra tion in creased sig nifi cant ly (P < O·OO I) to 11 3 ± 15 mM . Subsequ entl y the lac tose co ncentra tio n co ntinu ed to in crease g radu a ll y to 132 ± 18 mM a t two days postpartum. Th e stee p , sig nifi ca nt in crease in m a mm a ry secre ti o n lactose co nce ntra tio n whi ch occurred a t three d a ys pre-partum was coin cid ent with th e pea k m a mm a ry o utput of oes tra dio l-17{3 a nd cessa ti on of th e m a mm a ry o utput of PGF"' into th e venou s dra in age. Also a t this tim e th e udd e r of each of th e cows was o bse rved to be lea king mi lk, indi ca ting th a t copi o us mi lk secre tio n had begun . In th e shee p th e ma mm a ry secre ti on con ce ntra ti o n ofl actose in creased s teadil y fro m 64 ± 9 to 73 ± 12 mM ove r th e p eri od six d ays pre-partum until two d ays pre-partum . Th ere was th en a slight in crease to 86 ± 7 mM 12 h pre-partum, follo wed by a furth er sig nifi cant (P < O·OI ) increas e to 122 ± 6 mM 12 h postpartum. In th ese a nim a ls th e p ea k ma mm a ry secretion of oes tradiol-17{3 a nd th e cessa tio n of ma mm a ry secre ti o n of PGF"' into th e venous drain age preced ed th e m aj o r in crease in ma mm a ry secreti o n conce ntrat io n of lactose whi ch occurred 12 h postpartum in associa ti o n with th e o nse t of copio us milk sec re tion . DI SCUSS I ON
A sig nifi ca nt ma mm ary secre tio n ofoes tradio l- 17{3 a nd PGF"' into th e veno us dra in age was o bse rv ed pre-partum in cows a nd s hee p. Thu s, in a dditi o n to th e ma mm a ry tra nsfer ofh o rmon es from blood to milk (H ea p , H a mon & F leet , 1982) , secreti o n o f end ocrine subs ta nces, o rig inating within th e m a mm a ry gla nd , into th e ve no us dra in age has now bee n d e mons tra ted pre-partum for three m aj or d a iry rumin a nts; th e co w a nd shee p , as desc ribed in th e prese nt s tud y, a nd th e goa t (M a ul e W a lk er & Pea ke r, 19 78, 1980 ). Pros tagla ndin s a re no t ge nera lly beli eved to be s tored by ti ss ues Uo uvenaz et al., 1970 ; Poyse r, 1972) a nd the net m a mm a ry o utput ofPGFa into th e ve no us pl as m a m a y be inte rpreted as indi ca ting th a t th e ma mm ary gla nd s of th ese three rumin a nts sy nth es ize PG F"' in la te pregn a ncy. Th e m a mm a ry sec re ti o n of oes tradi ol- 17{3, howeve r, m a y be th e produ ct of lysis of th e co nju ga ted s teroid ra th er th a n end oge no us sy nth es is, being d eri ved from hydro lys is in th e ma mm a ry gla nd of th e co njuga ted s te ro id , th e circu la ting conce ntra ti o n of whi c h g rea tl y exceed s th a t of un co nju ga ted oest roge ns in la te preg na ncy (\'\1o ng et al .. 1972; T sa ng, H ac ke tt & T urn er, 1975; Ro be rt so n & King, 1979). Th e tempo ra l pa ttern of th e ma mm a ry sec reti o n of oes trad iol- 17{3 a nd PGF"' d iffe rs be tw ee n the cow a nd th e shee p but correla tes well with th e cha nges in th e ma mm ary secre ti o n co nce ntra ti o n o f lac tose in each case. Altho ug h so me cha nges in lac tose co nce ntra ti o n occ ur ea rlier th a n th e peri od st udi ed here, the sha rp, sig nifi ca nt
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I3RI T I SH V ETER I NA RY J OU RNA L, 139,2
in creases in lactose concentra tion obse rv ed cl ose to parturiti o n were assoc ia ted with the onse t of copi ous milk secreti on in every case . A simil a r correl a ti o n betwee n cha nges in ma mm ary secret ion co ncen trat ion of lactose cl ose to term a nd th e onse t of co pi o us milk secret ion has bee n o bserv ed in goa ts (' lac toge nes is S tage II ', Fl ee t et a/., 19 75). Of the three rumin a nts und er co nsid era ti on these cha nges occ ur la tes t in th e shee p, neith er th e in crease in ma mm a ry secre ti on co nce ntra ti on of lactose , nor th e o nse t o f co piou s milk secreti on occurring un til imm edi a tel y post parlwn . T hu s th e tempo ra l pa ttern of th e m a mm a ry sec reti on ofPGFa a nd oes tra diol - 17{3 into th e veno us pl as m a shows a simil a r progress ion a mong th ese rumin a nts, th e cha nges occ urring ea rli es t in th e co w a nd la tes t in the sheep, the goa t fa lling between the two (M a ul e W a lker & Pca ker, 19 78 , 1980 ). Th e lac togeni c res pon se to pre- pa rtum milking whi ch occurs in th e cow, goa t a nd shee p (Roo k & Wh eelock, 196 7; Linze ll & Pea ker, 19 74; M a ul e W a lk er, Stewa rt & Th ompso n, 1982 ) is s uggested to be du e to th e remova l o f a n endoge no us loca lly-ac tiv e inhibitor p resent in pre-partum m a mm a ry secreti ons (Lin zell & Pea ker, 1974·) for whi ch a pros tagla ndin would be a good ca ndid a te (see M a ul e W a lk er & Pea ker, 198 1). T rea tm ent with a PGFa a na log ue (M a ul e W a lker & Pea ker, 1980) or inhibiti o n o f ma mm a ry pros tagla ndin synth es is (M a ul e W a lker , 1982 ) bo th di s rupt th e no rm a l pa ttern of lactoge nes is. Apa rt from th e well-d oc um ented effects of oestrogen o n ma mm a ry g rowth (see C owi e, Fo rsy th & H a rt, 1980) a nd prol ac tin secreti on (Ni swend er el aL., 1969; C ha n & M cites, 19 70), oes trogens a nd PGFa a rc fr equ ently cl ose ly associa ted in cascad e types of co ntrol sys tems (H orton & Poyse r, 19 76; Flint et al., 19 78; Poyse r, 198 1) a nd su ch interac ti ons ma y be prese nt in the ma mm a ry g la nd . Th e ini tiat ion of lactogenes is is closely related to th a t of pa rturiti on, but th e mecha ni s ms of th e indu ctio n of pa rturiti o n a nd in pa rti cul a r th e ex tent of reli a nce on th e corpu s luteum as a so urce of proges tero ne differs s ubs ta nti a lly betw ee n th e cow, goa t a nd s hee p (sec Na th a ni elsz, 19 78) . In contras t to th e differences in th e mec ha ni s m of indu cti on of pa rturiti on , th e prese n t st udy d emo nstra tes th a t cha nges in ce rta in ma mm a ry end ocrin e- type secreti o ns a re co mm o n to a ll three s pec ies a nd th a t th e temporal rela ti ons hip betwee n these end oc rin e secretions a nd th e o nse t of co pi o us milk secreti on a re cl osely simil a r. Th e res ults co nfirm th e co nce pt of th e ma mm a ry g la nd as a n end ocrine gl a nd a nd support th e h ypo th es is th a t th e rela ti ons hip betw ee n ma mm a ry secreti o n of pros tagla ndin s a nd oes troge ns, a nd th e co ntro l of lac toge nes is may co ns titut e a comm on loca l mec ha ni sm in th ese three rumin a nts th a t is fund a mental to the ini tia tio n of copi ous milk sec ret ion .
:\CK NO WL EDC El\·1ENTS
Th e a uth ors a re g ra teful to Dr R . B. H ea p for hi s enco urage ment a nd su rgica l assi s ta nce a nd to M r R . Pro udfoot, Mr A. Bu cke, Mr A. C owi e a nd Mr T. Pea rson fo r ca re o f th e a nim a ls. REFERE!'\CES
R. G., HEAP , R. 13 . & II.I .I NG \\'ORT H , D. V. ( 197 1).Joumal oj£ndocrinology 5l, 1333. L. & !VIEJTES, j. ( 1970). Endocrinolog;• 86, 503. CO WI E, A . T., F O RSYTH , I. A . & HART , I. C. ( 1980). M onograjJI/SO II Endocrinolog;• 15, 11 0. C H A I.I. I S, .J . C HEN, C .
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FLEET , I. R ., LI NZELL, j. L. & PEAKER, M . ( 1972) . British Vete rinary j ouma /128, 297 . FL EET, I. R ., GOODE, j . A., H AMON, M . H ., L AUR I E, M . S., LI NZEL L, .J . L. & PEA KER, M . ( 1975) . .Joumal of Physiology 251, 763. F LINT, A . P. F., K INGSTON, E. j. , ROB INSON, j . S. & T HORBURN, G. D . (1978) . j oumal of Endocrinology 78, 367. H EAP, R . 13 ., H AMON, M. H . & FLEET, I. R . ( 1982). British Veterinary j ouma/ 138, H ORTON, E . \ '\' . & PO YSER, N . L. ( 1976). Physiological Reviews 56 ,595 . .J OUVEN:\7., G. H ., NUGTEREN, D . H ., 13EERTH UIS, R . K . & V AN DOR P, D. A. ( 1970). Biochimica et bioph)'sica ac/a 20 2, 23 1. Ll NZELL, .J . L. ( 1960). j ounwl of Physiology 153, 4-92 . L1 N7.E LL , J. L . ( 1966) . Circulation Research 18, 745. LI NZE LL, .J . L. & PEAK I::R, M . ( 1974). J oumal of Physiolog;• 243, 129. LI NZE LL, J. L. & R,\ SM USSEN, F . ( 1972). In J-landbuch tier Tieremiilmmg 2, cd. VV . L cnkci 1 an d K . 13rcircn, p. 203. H amburg: Paul Par cy. M AU LE W ALK ER, F . M . ( 1982) . .Joumalof Physiology 325, 7 1P. !VI."U LE W ALKE R, F. M . & PEAKER, M . ( 1978) . j oumalof Ph}'siolog;• 284, 71P. l'v L\U LE W ALKER, F. M . & PEA KER, M . ( 1980). j oumal of Physiology 309, 65. !VI AU I.I' W ALKER, F. M . & PEA K ER, M . ( 198 1). ,1cta vete rinaria scandinavica Su pp l. 77, 299 . l'v! AU LE W ALKER, F. l'v l. , STEWART, H . J. & T H 0 ~1PSON, G . E. ( 1982) . .Journal of Ph]•Siology 325, 72 P. N AT H,\ N1ELSZ, P. V•i. ( 1978). Annual Review of Phpiolog;• 40, 4- 1 I . N ISWI·:NDER , G . D ., C HEN, C. L. , MI DGE LEY, A . R ., M EITES, j . & E LLI S, S. ( 1969). Proceedings of the Society of Experimental Biolog;• and Medicine 130 , 793. POYSER, N . L. ( 1972). J ouma/ of Endocrinology 54, 14·7. P OYS ER, N. L. ( 198 1). Acta veterinaria scandinavicn Sup pl. 77 , 24 1. ROBERTSON, H . A. & K lNG, G. j. ( 1979). j oumal of Reproduction and Fertility 55, 463 . ROOK, .J . i\. F. & VVI-l!-:1-: LOC: K, .J. V . ( 1967) . .Joumal of Dail)' Research 34, 273. T SA!':C, C. P. W ., 1-1.-\CKF.rr, A . .J . & TURNER, E. M . ( 1975). Ca nadian.JoumalofA nimal Science 55, 509. W ONC , tv!. S. F ., Cox, R . 1. , CuRR I E, W . 13 . & T HORBUR:'\', G. D . ( 1972) . Proceedings of the 15th Annual Meeting of the F.ru/ocrine Society of ilustmlia, SJ•dney• 15, 8.
ENDOCRINE ACTIVITY OF THE MAMMARY GLAND: OESTROGEN AND PROSTAGLANDIN SECRETION BY THE COW AND SHEEP MAMMARY GLANDS DURING LACTOGENESIS
BY F. M . MAULE WALK ER,
A. j . DAVI S AND I. R.
FLEET
Agricultural Research Council Institute of Animal Physiology, Babraham, Cambridge CB2 4A T .
SU MMARY
M a mm ary venous and ca rotid arterial plas m a concentrations of oestradiol-17{3 a nd prostagla ndin Fa (PGF a), a nd mammary secre tion co ncentrations of lactose were d ete rmin ed in three j ersey cows and four Friesland sheep from seven d ays pre-partum until two days post partwn. Sign ifi ca nt mammary secretion of oes tradiol-17{3 a nd PGFa into th e venous drainage was observed in both cows a nd sheep pre-partum, supporting the hypo th es is postul a ted for th e goat that th e m a mm ary g la nd is a n e ndocrin e organ . The timing of th e onset of co pious milk secre ti on, co in cid ent with a n increased m a mm a ry secretion co ncentration of lactose (lactogenesis), differed between cows a nd sheep in relation to parturition. H oweve r, th e tempora l pa ttern of cha nges in the mamm a r y secret ion of oes tradiol-17{3 a nd PGFa, in relation to lactoge nesis, was simil ar in th e two spec ies; a cessa ti on of m a mm a ry secretion of PGFa a nd a transient peak in th e ma mm a ry secretion of oestradiol-17{3 occurrin g imm edi ate ly pri or to th e onset of cop io us milk secretion . This relationship is similar to that o bserved prev iou sly in the goa t, a nd indi cates co mm on mechanisms fo r the co ntrol of lactoge nesis in these three ruminants which h ave differing e nd ocrinol ogical profiles associated with th e m a inte na nce of pregnancy a nd co ntrol of pa rturiti on .
I NTRODUCT I ON
Earlier st udi es in goats (Mau le W al ke r & Pcaker, 1978, 1980 ) d e mons tra ted substa nti a l mammary secre ti on of oes trad iol- 17{3 a nd produ cti on of prostaglandin Fa (PGFa) during la te preg na ncy. The secret io n of PGFa a nd oest radiol-17{3 into the mammary venous pla sma in creased to peak va lu es pre-partum a nd subseq uently decl in ed to undetectab le leve ls cl ose to parturition, in assoc ia ti on with the onset of co piou s milk secretion. Inhibiti o n of ma mm ary prod uction of prostagla ndin s disrupts the co urse of lactogenes is in this spec ies, but ca n be overcome to so m e ex tent by the
172
BRITISH VETERINARY .JOURNAL, 139, 2
administration of exogenous oestrogen (Maule Walker, 1982) . The present study was undert a ken in two other dairy ruminants, the Jersey cow and th e Friesland sheep, which show a different temporal pattern in the relationship between lactogenes is a nd parturition compared with the goat. The aim was to establish whether the mammary glands of these rumin a nts show endocrine activities simi lar to those observed in th e goat in relation to the onset of copious milk secretion .
MATERIALS AND i'viETHODS
Three jersey cows and four Friesland sheep were surgically prepared for the collection of arterial and mammary venous blood by the methods d escribed by Linzell ( 1960) for goats with a carotid artery and a 'milk' (caudal superficial epigastric) vein exteriorized in skin-covered loops. At the start of these studies th e cows were in their fourth to seventh pregnancies and the sheep were in their second to fifth pregnancies; the exact stage of gestation was known for a ll animals. Milking had ceased approximately 14 weeks (cows) or 10 weeks (sheep) prior to parturition. P a rturition occurred in the cows between 281 and 284 days gestation, and in the sheep between 144· a nd 14·7 clays gestation. All young were born alive and survived to wea ning . The young were removed as soon as possible a nd routine twice-daily milking begun . The period studied was from seven d ays pre-parium until two d ays post parlwn . Pa ired carotid arterial a nd mammary venous blood samples we re ta ken between I 0.30 a nd 11 .30 h daily . The sheep were sampled slightly more frequently than the cows, a n additional sample be ing obtained approximately 12 h pre-partum. Coagulation of bl ood samples was prevented by the addition of heparin (10 to 15 units/ m l blood) . Mammary b lood samples were collected and mammary blood flow was determin ed by continuous thermodilution (Linzell, 1960, 1966 ; Linzell & R as mussen, 1972) while the animal was standing and the external pudic vein at the base of th e udder was compressed manu a lly ; this was done to obtain tru e mammary venous blood (Linzell, 1960 ; Linzell & R as musse n, 1972) . In some of th e s hee p th ere was a small mid-lin e superficial epigastric vein in addition to th e ' milk' vein exteriorized in a skin loop. In th ese an imals this mid -lin e ve in was a lso m a nually compressed. After re mova l of a small sample for the det ermination o f pac ked cell volume (PCV ), blood was immedi a te ly centrifuged a t 4°C and the pl as m a stored at -20°C until a nalysed. Prior to parturition small (I to 2 ml) samples of mammary secretion we re ta ken by hand milking ase ptically . Larger volumes of mammary secretion were no t taken jJre-parlum since thi s ca n indu ce premature lac togenes is in sheep (Maule W a lk e r , Stewart & Thompson, 1982) a nd cows (sec Roo k & Wh ee loc k, 1967) . Pos t- pa rtum samp les of milk were ta ke n from pooled mid-milk obta in ed at rou tin e milkin g. Pl as m a samp les were a nalysed for prost ag la ndin F, (Maule W a lk e r & Pca kcr, 1980) an d oes tradio l-17{3 (C ha lli s, He a p & Illin gwo rth , 1971 ). Samples of m a mm a ry sec re ti o n were a nalysed for lac tose by th e m et hod of Fl ee t, Lin zc ll & Pea kcr ( 1972). Student's /-t es t was used to tes t th e statistical s ig nifi ca nce of paired data .
RE SU lTS
The carotid a rt eria l and mammary ven o us plasma co nce ntra tion s of PCf" and
ENDOCRINE ACTIVITY OF THE MAMMARY GLAND
173
oestradiol-17/3 from seven days pre-partum to two days post parium for the cows and sheep a re presented in Figs I a nd 2, respectively . PCJ~
In both the cows and sheep the mammary venous plasma concentration of PGF<> was significantly greater (P
wo Plasma proslaglandin Fa
pg/ml
300
200
100
CA 0 Plasma oestradiol · 171l pgiml
~00
J
300
200 MV
l/ 100
, j,-
v }/
\
\
''L_~ \ I I
'\ I
0 Time from parturition days
Fig . \ . The con ce ntra tion of prosta glandin F0 and oes tradiol- 17{3 in mammary venous (l'v!V ) an d carot id a rt eria l (C i\ ) plasma in three j ersey cows from seven days pre-parium until two days poslfwrlwn. V a lu es arc mean :t SEM . MV p lasma ·· • •• • ··, Ci\ pla sma - -• - -• - -.
174
BRITISH VETERINARY JOURNAL, 139,2 n:t.
1100 Plasma prostaglandin pg/ml
Fa 10°0
y1
900 500
1.00
I
I
300
200
t~~~-rA
I
100
Plasma oestradiol -17 iJ pg/ml
90
,j,
80
I I
70
I I I I
60
I I I
50
LO
I I
I
)
30
I I
20
~
;¥
1 -6
5
3
2
0
2
3.
Time fro m parturition days
Fig . 2. The concen trations of prostag landin F0 a nd ocstrad iol-1 7{3 in mammary ve nous (M V) and caro tid a rt er ia l (CA) plasma in four Friesland sheep from six days Jm-partum until two day s fJos/ par/tan . Valu es a rc means :!: SEM . MY plas ma -- • -- • -- , CA plasma - -• - -• - -
Oestradiol- I 7{3 The m a mm a ry venous co nce ntra tion of oestrad iol-! 7{3 in both th e cows a nd shee p was sign ifi cantly (P<0-0 l ) greater than that of th e carot id a rt eria l p las m a fro m seve n d ays until four days pre-partum . After adju s tm ent for mea n mammary plasma fl ow during thi s time , m a mm ary output of PGFa into th e veno us p las ma of th e cows and sheep was 167 ± 44 a nd l-3 ± 0·4 ng/ min , respect ively. In th e cows th e mammary ou tput of oest rad iol-17{3 in to th e venous p lasma in creased sig nifi ca ntly (P < 0-001) a t three days pre-pa rtum to 530 ± 130 ng/min, decreasing dramatically thereafter, the output at term bein g 56± 18 ng/mi n . I n the shee p , m a mm ary venou s p lasma co nce ntra ti ons of oes tradio l- 17{3 were not sig nifi ca ntl y different from those of carotid a rt eri a l pl as m a from three to two days prepartum . Howeve r a peak in th e m a mm a ry output of oes tra di o l-17{3 into the venous
ENDOCRI N E ACTIVITY OF TH E M AMM ARY G LAN D
175
dra in age occurred one day pre-partum, th e m ea n va lue being 9·4 ± 0·8 ng/ min . At thi s tim e th e ca ro tid a rteri a l plasm a con centra ti o n in creased , was ma inta in ed unt il 0· 5 d ay pre-partum, a nd fell th erea fter . M a mm a ry output of oes tradi ol-17{3 into th e veno us dra in age ceased at 0·5 d ay pre-partum a nd re m a in ed a bsent over th e res t of th e tim e studi ed.
J\1ammmy secretion lactose concentrations In the cows the la ctose co nce ntra ti o n 111 th e ma mm a ry sec re ti o ns in crea sed g radu a ll y from 64 ± 12 to 71 ± 5 m M ove r th e peri od of seven to four d ays pre-partum . At three d a ys pre-partum th e co nce n tra tion in creased sig nifi cant ly (P < O·OO I) to 11 3 ± 15 mM . Subsequ entl y the lac tose co ncentra tio n co ntinu ed to in crease g radu a ll y to 132 ± 18 mM a t two days postpartum. Th e stee p , sig nifi ca nt in crease in m a mm a ry secre ti o n lactose co nce ntra tio n whi ch occurred a t three d a ys pre-partum was coin cid ent with th e pea k m a mm a ry o utput of oes tra dio l-17{3 a nd cessa ti on of th e m a mm a ry o utput of PGF"' into th e venou s dra in age. Also a t this tim e th e udd e r of each of th e cows was o bse rved to be lea king mi lk, indi ca ting th a t copi o us mi lk secre tio n had begun . In th e shee p th e ma mm a ry secre ti on con ce ntra ti o n ofl actose in creased s teadil y fro m 64 ± 9 to 73 ± 12 mM ove r th e p eri od six d ays pre-partum until two d ays pre-partum . Th ere was th en a slight in crease to 86 ± 7 mM 12 h pre-partum, follo wed by a furth er sig nifi cant (P < O·OI ) increas e to 122 ± 6 mM 12 h postpartum. In th ese a nim a ls th e p ea k ma mm a ry secretion of oes tradiol-17{3 a nd th e cessa tio n of ma mm a ry secre ti o n of PGF"' into th e venous drain age preced ed th e m aj o r in crease in ma mm a ry secreti o n conce ntrat io n of lactose whi ch occurred 12 h postpartum in associa ti o n with th e o nse t of copio us milk sec re tion . DI SCUSS I ON
A sig nifi ca nt ma mm ary secre tio n ofoes tradio l- 17{3 a nd PGF"' into th e veno us dra in age was o bse rv ed pre-partum in cows a nd s hee p. Thu s, in a dditi o n to th e ma mm a ry tra nsfer ofh o rmon es from blood to milk (H ea p , H a mon & F leet , 1982) , secreti o n o f end ocrine subs ta nces, o rig inating within th e m a mm a ry gla nd , into th e ve no us dra in age has now bee n d e mons tra ted pre-partum for three m aj or d a iry rumin a nts; th e co w a nd shee p , as desc ribed in th e prese nt s tud y, a nd th e goa t (M a ul e W a lk er & Pea ke r, 19 78, 1980 ). Pros tagla ndin s a re no t ge nera lly beli eved to be s tored by ti ss ues Uo uvenaz et al., 1970 ; Poyse r, 1972) a nd the net m a mm a ry o utput ofPGFa into th e ve no us pl as m a m a y be inte rpreted as indi ca ting th a t th e ma mm ary gla nd s of th ese three rumin a nts sy nth es ize PG F"' in la te pregn a ncy. Th e m a mm a ry sec re ti o n of oes tradi ol- 17{3, howeve r, m a y be th e produ ct of lysis of th e co nju ga ted s teroid ra th er th a n end oge no us sy nth es is, being d eri ved from hydro lys is in th e ma mm a ry gla nd of th e co njuga ted s te ro id , th e circu la ting conce ntra ti o n of whi c h g rea tl y exceed s th a t of un co nju ga ted oest roge ns in la te preg na ncy (\'\1o ng et al .. 1972; T sa ng, H ac ke tt & T urn er, 1975; Ro be rt so n & King, 1979). Th e tempo ra l pa ttern of th e ma mm a ry sec reti o n of oes trad iol- 17{3 a nd PGF"' d iffe rs be tw ee n the cow a nd th e shee p but correla tes well with th e cha nges in th e ma mm ary secre ti o n co nce ntra ti o n o f lac tose in each case. Altho ug h so me cha nges in lac tose co nce ntra ti o n occ ur ea rlier th a n th e peri od st udi ed here, the sha rp, sig nifi ca nt
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I3RI T I SH V ETER I NA RY J OU RNA L, 139,2
in creases in lactose concentra tion obse rv ed cl ose to parturiti o n were assoc ia ted with the onse t of copi ous milk secreti on in every case . A simil a r correl a ti o n betwee n cha nges in ma mm ary secret ion co ncen trat ion of lactose cl ose to term a nd th e onse t of co pi o us milk secret ion has bee n o bserv ed in goa ts (' lac toge nes is S tage II ', Fl ee t et a/., 19 75). Of the three rumin a nts und er co nsid era ti on these cha nges occ ur la tes t in th e shee p, neith er th e in crease in ma mm a ry secre ti on co nce ntra ti on of lactose , nor th e o nse t o f co piou s milk secreti on occurring un til imm edi a tel y post parlwn . T hu s th e tempo ra l pa ttern of th e m a mm a ry sec reti on ofPGFa a nd oes tra diol - 17{3 into th e veno us pl as m a shows a simil a r progress ion a mong th ese rumin a nts, th e cha nges occ urring ea rli es t in th e co w a nd la tes t in the sheep, the goa t fa lling between the two (M a ul e W a lker & Pca ker, 19 78 , 1980 ). Th e lac togeni c res pon se to pre- pa rtum milking whi ch occurs in th e cow, goa t a nd shee p (Roo k & Wh eelock, 196 7; Linze ll & Pea ker, 19 74; M a ul e W a lk er, Stewa rt & Th ompso n, 1982 ) is s uggested to be du e to th e remova l o f a n endoge no us loca lly-ac tiv e inhibitor p resent in pre-partum m a mm a ry secreti ons (Lin zell & Pea ker, 1974·) for whi ch a pros tagla ndin would be a good ca ndid a te (see M a ul e W a lk er & Pea ker, 198 1). T rea tm ent with a PGFa a na log ue (M a ul e W a lker & Pea ker, 1980) or inhibiti o n o f ma mm a ry pros tagla ndin synth es is (M a ul e W a lker , 1982 ) bo th di s rupt th e no rm a l pa ttern of lactoge nes is. Apa rt from th e well-d oc um ented effects of oestrogen o n ma mm a ry g rowth (see C owi e, Fo rsy th & H a rt, 1980) a nd prol ac tin secreti on (Ni swend er el aL., 1969; C ha n & M cites, 19 70), oes trogens a nd PGFa a rc fr equ ently cl ose ly associa ted in cascad e types of co ntrol sys tems (H orton & Poyse r, 19 76; Flint et al., 19 78; Poyse r, 198 1) a nd su ch interac ti ons ma y be prese nt in the ma mm a ry g la nd . Th e ini tiat ion of lactogenes is is closely related to th a t of pa rturiti on, but th e mecha ni s ms of th e indu ctio n of pa rturiti o n a nd in pa rti cul a r th e ex tent of reli a nce on th e corpu s luteum as a so urce of proges tero ne differs s ubs ta nti a lly betw ee n th e cow, goa t a nd s hee p (sec Na th a ni elsz, 19 78) . In contras t to th e differences in th e mec ha ni s m of indu cti on of pa rturiti on , th e prese n t st udy d emo nstra tes th a t cha nges in ce rta in ma mm a ry end ocrin e- type secreti o ns a re co mm o n to a ll three s pec ies a nd th a t th e temporal rela ti ons hip betwee n these end oc rin e secretions a nd th e o nse t of co pi o us milk secreti on a re cl osely simil a r. Th e res ults co nfirm th e co nce pt of th e ma mm a ry g la nd as a n end ocrine gl a nd a nd support th e h ypo th es is th a t th e rela ti ons hip betw ee n ma mm a ry secreti o n of pros tagla ndin s a nd oes troge ns, a nd th e co ntro l of lac toge nes is may co ns titut e a comm on loca l mec ha ni sm in th ese three rumin a nts th a t is fund a mental to the ini tia tio n of copi ous milk sec ret ion .
:\CK NO WL EDC El\·1ENTS
Th e a uth ors a re g ra teful to Dr R . B. H ea p for hi s enco urage ment a nd su rgica l assi s ta nce a nd to M r R . Pro udfoot, Mr A. Bu cke, Mr A. C owi e a nd Mr T. Pea rson fo r ca re o f th e a nim a ls. REFERE!'\CES
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