miparous (heifers) lactating Holstein cat- tle were used in a 112d study to exam- ine the effects of pattern of admin- istration of recombinantly derived bST.
Milk Yield of Dairy Cows Receiving Somatotropin (Somavubove) Daily with Periodic 14-Day Interruption EDWARD P. STANISIEWSKI, DAVID
M. MEEUWSE, LAVERN F. KRABILL, and JAMES W. LAUDERDALE
Performance Enhancement Research The Upjohn Company Kalamazoo, MI 49001
(Key words: somatotropin, milk yield, dairy cattle)
ABSTRACT
Thirty multiparous (cows) and 15 primiparous (heifers) lactating Holstein cattle were used in a 112d study to examine the effects of pattern of administration of recombinantly derived bST on 3.5% FCM yield. Ten cows and 5 heifers each received either no injection (controls), 14 mg of bST daily, or four repetitions of 14 mg of bST/d for 14 d followed by 14 d of no injection (intermittent bST). Because there was an interaction between treatment groups and parity, analyses were performed separately for cows and heifers. All cows and heifers produced more FCM when given bST than controls. Comparing FCM only during the last 7 d of each period of injection for the intermittent bST group with contemporary daily injected cattle indicated that cows produced equivalent amounts of milk at those times, whereas heifers given daily bST produced 3.4 kg/ d more than intermittently injected animals. Furthermore, over each of the four repetitive periods, cows and heifers given daily or intermittent bST responded similarly, although heifers given continuous bST produced more FCM than the intermittent group during each of periods 2 through 4. We conclude that daily administration of bST lends itself to dosing termination during established lactation with concomitant decline of FCM; resumption of bST allows milk yields of cows to achieve levels comparable with those prior to short-term interruption.
Received April 3, 1990. Accepted July 22, 1991. 1991 J Dairy Sci 74:4195-4201
Abbreviation key: MED = maximum equivalent difference test, PRE = average daily 3.5% FCM during the 5 d prestudy, WFCM = average daily 3.5% FCM over d 8 to 14 of each 14-d bST injection period, P14FCM = average FCM difference from control during each 14-d bST injection period, TFCM = average daily 3.5% FCM over the total duration of study. INTRODUCTION
Lactating dairy cows injected with pituitaryderived or recombinant bST had increased milk yields of 2.2 to 11.4 kg/d over uninjected controls (2, 13, 14, 15). Milk yields increase rapidly in response to bST and then stabilize (7, 13). Similar responses were detectable in short-term studies (The Upjohn Company, unpublished observations) in which initial milk yield increased beginning 1 or 2 d after commencement of bST administration, reached a plateau after about 4 to 6 d of treatment and then declined to control values within about 5 d after cessation of bST. Furthermore, results of a dose titration field study with lactating dairy cows (1) indicated that a dose of 13.6 to 16.6 mg of bST/d is sufficient to achieve an approximate plateau of milk yield response. Therefore, we selected a daily dosage of 14 mg of bST for further study. Under practical commercial dairy conditions, intemption of daily administration of bST to certain cows may become necessary. This may occur for a variety of reasons, such as during mastitis treatment, hot weather, or other times when management determines that the burden of producing milk should be reduced. We, therefore, wanted to examine milk yield responses of dajl cows given bST 4195
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STANISEWSKI ET AL.
d postpartum on the day of assignment to this study. Multiparous and primiparous cows were each blocked based on postpartum interval. There were 10 multiparous and 5 primiparous animals per treatment group. The animals of each replicate were assigned, within parity (multiparous versus primiparous), randomly to one of three experimental groups: 1) daily, 14 mg of bST daily for 98 d by syringe and needle injection followed by 14 d of no bST injection (112 d total); 2) intermittent, four repetitions of 14 mg of bST daily for 14 d by syringe and needle injection followed by 14 d of no bST injection (112 d total); and 3) control, uninjected controls, monitored for 112 d. Cows given daily treatment were in second to sixth (mean = 3.1) parity and averaged 144 DIM at start of study, whereas cows on intermittent or control treatments were in second to fourth (mean = 2.5) parity and averaged 146 DIM or second to fifth (mean = 2.8) parity and averaged 144 DIM. Heifers (fist parity) averaged 162, 164, and 169 DIM at start of study for daily, intermittent, and control treatments. Somavubove is the proprietary name for The Upjohn Company ( K a l a m m , MJ) bST. Somavubove was stored at room temperature prior to reconstitution. Each vial of bST was reconstituted with sterile distilled water to produce a solution containing 14 mg of bST/ml. Cows receiving bST were injected with 1 ml of solution. A 3-ml disposable syringe and new 23-gauge by 1.9-cm needle were used for each cow. AU injections were made in the semitendinosus muscle (back of the leg). All cows receiving bST were injected daily by the herd owner while in the milking parlor during the a.m. milking procedure (0500 to 0800 h). Cows were identifled by a unique number via ear tag or neck chain; a leg band was used to MATERIALS AND METHODS alert the milkers that the cow was on study and that milk yield needed to be recorded. Animals and Treatments All cows in this herd were housed in freeThirty multiparous and 15 primiparous lac- stall barns with 24 h of supplemental lighting tating Holstein cows located at a 24O-cow in addition to natural lighting via windows and commercial dairy in Michigan were identified open sides. AU cows in this herd were sorted by the owner for use on this study. This herd into one of two groups by level of yield and had a rolling herd average of 9435 kg, and fed to yield a TMR composed of forage (60% cattle had not previously been given exoge- haylage, 40% corn silage); 5.4 or 6.8 kg/d of nous bST. Cows were free of metabolic disor- high moisture corn; 4.5 kg/d of dry corn, brewders, mastitis, and medication upon assignment ers grain, and distillers grain, .15 kg/d of liquid to this study. Cows were between 99 and 235 fat; and 2.3 kg/d of a 35% soy mineral mix in in an interrupted pattern to determine to what degree increased milk yield can be resumed after bST interruption. Available milk yield data from cows given bST for consecutive lactations indicate no lactation by bST interaction (5, 9, 10, ll), reduced subsequent lactation response at some bST doses ( l l ) , or enhanced subsequent lactations (8). This suggests a minimal, if any, carry-over effect on the response of cows to bST when those cows received long-term bST administration, followed by intemption of bST during the dry period, and then resump tion of bST during the ensuing lactation. Furthermore, Eppard et al. (7) established a milk yield dose-response curve for six doses of pituitary-derived bST using a Latin square design with 1 0 4 treatment periods and intervening 4 d periods of no treatment, indicating that responsiveness is maintained with short-term bST interruption. In addition, lactating dairy cows given sustained-release bST every 28 d exhibited cyclic patterns of milk yield response during which milk yields were significantly elevated every 2nd wk after a treatment (12). Greatest responses occurred, however, after fist and second treatments but were less pronounced with subsequent bST treatment. Furthermore, administration of sustained-release bST every 14 d also results in cyclical milk yields with a progressive yield increase over 1- to 7 4 postinjection and progressive decrease over 9 to 14 d (3). However, waning of milk yield response was not apparent over 18 injection intervals (3). The objective of this study was to determine the effect of repeated interruption of bST administration on milk yield of lactating dairy cows during one lactation.
Journal of Dairy Science Vol. 74, No. 12, 1991
SOMATOTROPIN, MILK YIELD, AND DAIRY CA'ITLE
five feedings per day, Routine biweekly veterinary service and herd health maintenance were provided by the herd veterinarian. The 45 cows assigned to the study remained integrated with cattle not on study. Milking was at 0500 to 0800 h and 1630 to 1930 h in a double10 herringbone milking parlor. Germania milk receiver jars (DHI approved) calibrated in .045-kg increments were used to measure individual cow milk weights at a.m. and p.m. milking for each cow from 5 d before the study and during the 112d experimental period. Milk weights at each milking were recorded for study cows on forms provided. Milk yield was adjusted to 3.5% FCM (18, 19) based on the mean of four consecutive (November, December, January, and February) DHI milk fat records contemporary to the study. Statistlcal Analysls
Average daily FCM for each cow was computed for the 5 d preinjection @'RE), for the total duration of the study (d 1 to 98 of injection; TFCM), and for the 14 d postinjection. In addition, average daily FCM for each cow over d 8 to 14 of each 14-d injection period (d 8 to 14, 36 to 42, 64 to 70, and 92 to 98 on study) was calculated and denoted as WFCM. Days corresponding to F7FCM are coincident with achievement of a plateau in FCM response to bST. The difference in average daily FCM between controls and each of the bSTtreated cows during d 1 to 14,29 to 42, 57 to 70, and 85 to 98 was computed and denoted as P14FCM. Days corresponding to P14FCM are coincident with ascending FCM response to bST as well as the response plateau. Covariance analysis using PRE as the covariate was done for F7FCM and TFCM. Among groups, tests for homogeneity of slopes of PRE versus WFCM and PRE versus TFCM were performed. No covariate was used in the analysis of P14FCM. Furthermore, F7FCM and Pl4FCM were analyzed for differences among time periods using repeated measures methodology. For P7FCM. the linear time by experimental group interaction (slope comparison) was tested to examine changes in response over time. All appropriate mean separation tests were done using the least significant difference test, and all analyses were done
4197
using the SAS general linear models procedure (16). In addition, biological equivalence was tested among treatment groups using the maximum equivalent difference WED) test (6). The MED comparison between experimental groups was considered to be an unimportant difference when it was less than 2.5 kg FCMf d. Data presented in tables are least squares means. Analyses were performed on specific sequences of days (e.g., WFCM), and mean FCM during those days were analyzed, reported, and interpreted as least squares means. Figures are provided as a visualization of d a y FCM patterns throughout the study, although analyses were not performed on specific day to day comparisons. Although least squares means are not available for figures, daily FCM in figures provides visualization of significant temporal relationships derived from analyses. RESULTS
Analyses of the slopes of preinjection period FCM versus injection period FCM of the experimental groups indicated that slopes were not significantly different using either TFCM, (P > .2) or P7FCM of intermittent injection periods (P > .2) data; thus, mean PRE FCM was an acceptable covariate. Parlly
Analysis of covariance using either TFCM or WFCM as the dependent variable indicated an interaction of treatment with parity (TFCM, P < .05 and F7FCM; P = .01). The R2 value was .84 to .85. Therefore, subsequent analyses are reported separately for multiparous (cows) and primiparous (heifers) animals. Comparison Between Cattle of bST-InJectedand Control Groups
Both cows and heifers given bST yielded more FCM (P e .01) than controls when compared over TFCM of study or WFCM of intermittent injections (Table 1; Figures 1 and 2). In addition, FCM was not equivalent between controls and UT-supplemented cows or heifers when compared using the MED test (Table 1). There was no difference (Table 1) in FCM J o d of Dairy Science Vol. 74, No. 12, 1991
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STANISIEWSKl ET AL.
TABLE 1. Least squares means for average daily 35% E M 1 of cows and heifers for the duration (98 d) of the study CrpCIvl) or over d 8 to 14 of each 1 4 4 bST injection period 0. TPCM Control
Dailv
P7FCM SEM
Intermiltent
~~~~~
Cod
25.p
31Sb
Heifer3
25.5'
32.0b
~~
~
.74
30.4b 27.0s
Control
.66
Dailv
Intermittent
SEM
31.5b 31.9b
32.Sb 28.5'
.72 .68
~
24.7' 25.3'
4b*cWithineach of TPCM and p7pcM,meaos with Merent superscripts within a row (parity) differ at P < .05. 'Days -5 through -f prestudy FCM used as a covariate. diflerence for comparison between two expeximental groups was 1.0 kg of P C M / ~thus, only ' ~ u equivalent m daily vmus inteamittent means w a e equivalent for F7PCM. 3Maximum @valent diffcreace test was 1.5 kg of XM/&thus, no comparisons were declared equivalent.
of cows given bST daily (31.5 kg/d) or in an intermittent (32.4 k@d) pattern when compared over the P7FCM duration of study, which corresponds to the 2nd wk of bST administration for cows receiving intermittent bST (Figure 1; P > .2). In fact, when compared during K'FCM, milk yields from cows were statistically equivalent (Table 1) between daily and intermittent groups. In contrast, heifers produced 3.4 kg/d more (P < .Ol) milk during P7FCM when given bST for the duration of study rather than intermittently (Figure 2). Comparison by MED indicated that milk yields of these groups were not equivalent. An overall effect of period for cows (P e .01) and heifers (P < .01) indicates a progression of declining FCM indicative of advancing
.I
0
I
11
11
In
II
as 86 I S Day on Study
42
70
TI
I 4
SI
II
106
111
Figure 1. Average daily 3.5% FCM of cows throughout days on study. Cows were uninjected controls (X), injected with bST intermirtcntly (e),or injected with bST daily (0). Journal of Dairy Science Vol. 74, No. 12. 1991
lactation (Figures 1 and 2). Animals of both parity groups given bST continually or intermittently did not respond differently over time when compared during WFCM intervals (P > .2) or during P14FCM (entire 2 wk of each injection period) intervals ( P > .2).A si@cant (P < .05) interaction of P7FCM period with treatment for cows suggests a difference in lactation slopes between bSTdosed and control cows that can be visualized in Figure 1. In contrast, a similar phenomenon is less apparent (P = -11) in heifers (Figure 2). Milk yield slopes during EY;IFCM declined less rapidly (P < .05) than for controls for both intermittent and daily bST groups of cows, whereas milk yield of P7FCM slopes between control
"-7
0
I
14
It
PL
W
42
Day
U
U
U
m
I4
II
,
SI
,
101 131
on Study
Pigum 2. Average daily 3.5%FCM of heifers throughout days on study. Heifers were uninjectcd controls 0, injected with hST intermittently (e),or injected with bST daily (0).
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SOMATOTROFTN, MILK YIELD. AND DAIRY CATIZE
and difference from control (P14FCM) for average daily 3.5% FCM TABLE 2. Least squares means absolute of cows and heifers daring specified periods during the study.' P7FCM Period
SEM Heifers Control Daily Inteamittent
SEM
57 to 70 d
...
...
...
...
6.1' 6.6' .36
7.P 7.4'
7.8' 8.P
8.2' 7.7'
85 to 98 d
64to 70 d
92to
27.5" 33.0b 33Zb .49
26.8' 33d 33.9b
23.4' 30.Sb 31Ab
21.2' 29Sb 30.4b
26.3' 31.2b 28.1ab
26.2' 33.6' 30.4b
25.4'
249
...
...
...
...
32.9 29.7b
319 28Sb
3.7' 2.6'
6.8' 4.8'
9.9' 6.9'
9.5= 7.2a
14 d
cows Control Daily Intdttent
P14FCM Period 29 to 42 d
lto 14 d
36to 42 d
ato
98 d
.55
.55
Isb*%thin parib, and for each FWCM and P14FCM period, meam with diffesent superscripts differ at P < .05. 'F7FCM = Average daily 3.5% FCM over d 8 to 14 of each 1 4 4 bST injection period, P14pcM = average FCM difference from control dnriog each 14-d bST injection period.
heifers and heifers given bST were parallel (P > .1). Using WFCM data, cows yielded similar (P > .2) quantities of FCM during each period on study when given bST daily or in an interrupted pattern (Table 2; Figure 1). Likewise, during period 1 (d 8 to 14), heifers of the group receiving daily bST had mik yield that was not significantly different from that of the intermittent group (Table 2, P = .11). There after, heifers given daily bST yielded more (P < .05) FCM during each of periods 2 through 4 than did heifers given bST intermittently (Table 2; Figure 2). When P14FCM data were used, FCM difference from controls was not different between daily and intermittent bST groups over each period, regardless of whether cows or heifers were examined (P > .2; Table 2). Poststudy Milk Yield
Differences in rate of return of FCM to control cow levels during the poststudy inter-
val were analyzed by regressing FCM on time (postinjection) and testing for lack of fit (Table 3) and heterogeneity of slopes (Table 4) among the FCM curves for groups of cows that previously received bST. Regression lines for daily milk yield showed no indication of lack of fit to a linear model for animals that were previously given clinical bST daily or bST intermittently (Table 3). The intercepts of these curves were not different, and slopes were homogeneous (Table 4; R2 = .14). Two animals did not complete the study. Both were assigned to the intermittent bST group. One cow was diagnosed (study, d 100) by the herd veterinarian as having incomplete rumen function, moderate ketosis, and suspected ulcer. Necropsy indicated an enlarged liver, numerous adhesions around the gall bladder, gastritis in the abomasum, and enteritis in the small intestine. This observation of one animal is insufficient to determine whether these problems were related to bST treatment. However, only data from 1 to 94 d on study were used from this cow. The second animal
TABLE 3. Test for lack of Linear fit mum daily 3.5% FCM for 1 to 14 d after last daily injection
LacL of fit
Experimental POUP
EMS1
Ms
F
P
R*
Daily bST Intermittent WT
13.67 26.48
14.44 13.77
1.06 .52
.40 .90
.23 .I3
'EMS =
~ r r o mean r sqmmi.
Journal of Dairy Science Vol. 74, No. 12. 1991
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STANISIEWSKI ET AL.
TABLE 4. Test for heterogeneity of slope of 3.5% PCM yield among experimental groups for the 14 d following last injection of IST.~ Analysis
df
Source Intercept Day Day x intercept* Enor
1 1 1
382
MS
F
P
.13 1120.3
.01 58.16
.94 .OOO1 .99
.m
.001
1926
R 2 = 14
q e s t null hypothesis of homogeneity of slopes. 1 ~ =2 correlation coefficient.
(heifer) removed had to be dried off to allow for a 60-d dry period; thus, only 84 d on study were completed. DISCUSSION
Data are presented that support the concept that administration of bST may be interrupted as desired, and, by 7 d after resumption of bST, FCM of cows returns to a yield equivalent to that which would temporally occur without intemption. However, FCM of heifers injected continually with bST was greater than that of intermittently treated heifers when compared using P7FCM. The reason for the different response between cows and heifers is unclear, but it may be related to the fact that heifers require higher bST dosing to achieve comparable FCM responses with that of COWS (1). The interruption intervals tested (14 d) may not provide adequate duration of blood titers of bST to elicit maximal FCM responses in heifers. Enhanced persistency of lactation has been recognized in cattle administered bST (2, 4). The fact that milk yield slopes during F7FCM were maintained in intermittently injected cows as well as daily bST-injected cows over controls is a novel observation. An interpretation of this observation would be that bST is having a residual effect on ability to produce milk after up to 14 d of interruption. In fact, some residual effect is likely because FCM of cows did not appear to return to control levels during periods of bST interruption (Figure 1). In contrast, FCM of heifers did appear to return to control quantities at bST cessation. Thus, residual effects from one bST period of injection to another in heifers seems less likeJournal of Dairy Science Vol. 74, No. 12, 1991
ly. Postpeak lactation curves of Holstein heifers are typically more persistent than that of Holstein cows (17), independent of exogenous bST. Lack of period by treatment interaction for heifers compared with that for cows may simply be that FCM of control heifers remained relatively constant in contrast to the decline of control cows (Figure 1 vs. Figure 2). CONCLUSION
Cattle administered bST produced more milk than contemporary controls. In addition,
daily administration of bST lends itself to dosing termination during established lactation with concomitant decline of FCM as dictated by cade management. Resumption of bST allowed cows to achieve milk yields comparable with those prior to short-term interruption. ACKNOWLEDGMENTS
The authors appreciate the assistance of Plover Vale Dairy personnel, V. N. Taylor for assistance with study design, D. L. Cleary for figure preparation, and M. S. McBride and K. H. Wagner for manuscript preparation. REFERENCES 1 Ash. K. A., J. F. McAllistex, V. N. Taylor, and J. W. Lauderdale. 1989. Estimation of the dose response to
bovine somatotropin for milk yield increase in lactating dairy cows. J. Dairy Sci. 72(Suppl. 1):428.(Abstr.) ZBanman, D.E., P. J. Eppard, M.J. DeGeeter, and G. M.Lam 1985. Responses of high producing dairy cows to long-term treatment with pituitary and recombinant somatotropin. J. Dairy Sci. 68:1352. 3Bauma11, D. E., D. L.. Hard, B. A. Choker, M. S. Partridge, K. Garrick. L. D. Sandles, H.N. Erb, S. E.
SOMATOTROPIN. MJLK YIELD, AND DAIRY CAl’TJ.E Ranson, G. P. Harmell, and R. L. Hhtz. 1989. Longterm evaluation of a prolonged-release formulation of N-methionyl bovine somatotropin in lactating dairy cows. J. Dairy Sci. 72642. 4Burton, J. H., G. K. Macled, B. W. McBride, J. L. Burton, K. Bateman, I. McMillan, and R. G. Eggert. 1990. Overall efficacy of chronically administered recombinant bovine somatotropin to lactating dairy cows. J. Dairy Sci. 73:2157. 5 Chalupa, W..A. Kutches. D. Swager, T. Lehenbauer, B. Vecchiarelli, R. Shaver. E. Robb, and D. Rock. 1989. Effects of supplemental somatotropin for two lactations on responses of cows in a commercial d a q . J. Dairy Sci. 72(Suppl. 1):327.(Abstr.) 6 Chester, S. T. 1986. Review of equivalence and hypothesis testing. Page 177 in Proc. Biopharmaceut. sect. Am. stat. Assoc., Chicago, E. 7 Eppard, P. J., D. E. Bauman, and S. N. McCutcheon. 1985. FBect of dose of bovine growth hormone on lactation of dauy cows. J. Dairy Sci. 68:1109. 8H~ber,J. T., J. L. Sullivao, S. Willman, R G. Hoffman, and G. F. Hartnell. 1990. Response of Holstein cows to biweekly sometribove (SB) injections for 3 consecutive lactations. J. Dairy Sci. 73(Suppl. 1): 157.(Abstr.) 9HUber. J. T., S. Willman, J. L. Sullivan. R. G. Hoffman, S. E. Framon, and K. S. Madsen. 1989. Milk yield response to somehibove, recombinant methionyl bovine somatotropin (S) during two consecutive lactations. J. Dairy Sci. 72(Suppl. 1:452.(Abstr.) lOMcBnde, B. W., J. L. Burton, J. H. Burton, G. K. Macled, and R Eggert. 1989. Multilactational treatment effects of rbST on production responses in lac-
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t a m Holstein MWS. J. Dairy Sci. 72(Suppl. 1): 43O.(Abstr.) 11 M m e k e , R. L., D. J. Schingoethe, D.P. Casper, W. A. Eisenbiesz, and R M. CleaIe. 1989. Lactational evaluation of recombinant bovine somatotropin for two consecutive lactations. J. Dairy Sci. 72(Suppl. 1): 551.(Abstr.) 12 Oldenbroek, J. K.,G. J. Garssen, A. B.Forbes, and L. J. Jonker. 1989. The effect of treatment of dairy cows of different breeds with recombinantly derived bovine somatotropin in a sustained-delivery vehicle. Livest. Rod.Sci. 21:13. 13 Peel, C. J., D. E. Bauman, R. C. Gorewit, and C. 1. Sniffen. 1981. Effect of exogenous growtb hormone on lactational performance in high yielding dairy cows. J. Nutr. 111:1662. 14Peel, C. J., T. J. Fro& D. E. Bauman, and R. C. Gorewit. 1983. meet of exogenous growth hormone in early and late lactation on lactational performance of dairy cows. J. Dairy Sci. 66:776. 15 Richard. A. L., S. N. McCutcheon, and D. E. Bauman. 1985. Responses of dauy cows to exogenous bovine growth hormone administered during early lactation. J. Dairy Sci. 68:2385. 16SAS@ User’s Guide: Statistics, Version 5 Edition. 1985. SAS Inst., Inc., Cary, NC. 17 Schuk, M.M., L. B. Hansen. G. R. Steuemagel, and A. L. Kuck. 1990. Variation of milk, fat, protein, and somatic cells for dairy cattle. J. Dairy Sci. 73:484. 18 Stoddard, G. E. 1980. How fat-corrected milk originated. Hoard’s Dairyman (Mar 10):319. 19Tyrrell, H.F., and J. T. Reid. 1965. Prediction of the energy value of cow’s milk. J. Dairy Sci. 48:1215.
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