Ž .
Ž .
intra-assay coefficients of variation were 10.5 n s 9 and 8.7 n s 4 , respectively. Ž
. The FSH assay used USDA bFSH B1 as the standard preparation Crowe et al., 1997 .
The sensitivity of the assay was 1 ng ml
y1
and the inter- and intra-assay coefficients of Ž
. Ž
. variation were 14.7 N s 5 and 13.7 n s 6 , respectively.
2.3. Statistical analyses One heifer, receiving 10.0 mg ODB by intramuscular injection, failed to show any
increase in plasma concentrations of E until 4 days following treatment and her
2
hormonal data was excluded from analyses. The E , and FSH data were subjected to
2
Ž .
repeated measures analyses of variance PROC GLM, SAS, 1989 followed by regres- Ž
. sion analyses SAS, 1989 . Because of the between animal variability, concentrations of
FSH were analysed as changes from pre-treatment concentrations.
3. Results
3.1. Plasma concentrations of E
2
All animals had similar and non-detectable concentrations of E pre-treatment. Peak
2
Ž concentrations of E
following all injection and intravaginal capsule treatments Table
2
. 1 were significantly higher than pre-treatment concentrations and those in untreated
Ž .
Ž . control animals Fig. 1 . The interval h from administration of ODB to peak E
2
Ž .
Ž .
concentration Table 1 was similar P 0.1 in heifers given intramuscular injections
Table 1 Effect of ODB administration using different doses and routes of administration on characteristics of plasma
Ž .
concentrations of oestradiol MeanS.E. in ovariectomised heifers given a progesterone intravaginal device Ž
. PRID
ODB No. Of
Pre-treatment Peak
No. of hours to No. of hours
No. of hours treatment
heifers Concentrations
Concentration reach maximum
to reach - 3 to reach -1
Ž .
Ž . Ž
. mg
n of E
of E pgrml
concentration of E pgrml of E
pgrml of E
2 2
2 2
2
Controls
a
0.0 3
0.1 0.10.05
Topical administration by intraÕaginal capsule
b ad
a a
5.0 4
0.1 3.87.1
25.54.2 54.023.8
72.019.4
b bd
a a
10.0 5
0.1 4.16.3
27.63.7 43.516.8
87.617.3 Intramuscular injection in 2ml corn oil
bc ac
a a
0.5 4
0.1 11.97.1
13.54.2 44.019.4
57.019.4
c ac
a ac
1.0 4
0.1 18.07.1
15.04.2 70.516.8
97.519.4
c c
a bc
2.5 6
0.1 24.35.8
11.03.4 82.013.7
125.015.8
d c
b bd
5.0 4
0.1 72.47.1
12.04.2 135.016.8
163.519.4
d ac
b d
10.0 4
0.1 84.68.2
18.04.8 158.019.4
188.022.4
a,b,c,d
Ž .
Within column, treatments with different superscripts are significantly different P - 0.05 .
Ž .
Fig. 1. Effect of different doses 0, 0.5, 1, 2.5, 5, and 10 mg of ODB dissolved in 2 ml of corn oil and administered by intramuscular injection to ovariectomised heifers at the time of PRID insertion on plasma
Ž . Ž
. concentrations of oestradiol pgrml
ns 3–6 heifers per dose .
Ž .
Ž .
mean 13.4 1.24 h , and was longer P - 0.05 in heifers given the 5 and 10 mg ODB Ž
. by intravaginal capsules
mean 25.5 2.84 h . Peak plasma concentration of E
2
Ž Fig. 2. Effect of different doses of ODB administered either by powdered form in a gelatine capsule 5- and
. Ž
. 10-mg doses attached to PRID and two doses 0 and 0.5 mg dissolved in 2 ml of corn oil and administered
by intramuscular injection to ovariectomised heifers at the time of PRID insertion on plasma concentrations of Ž
. Ž
. oestradiol pgrml in ovariectomised heifers ns 3–4 heifers per dose .
M. O’Rourke
et al.
r Animal
Reproduction
Science 59
2000 1
– 12
6
Table 2 Ž
. Effect of ODB administration using different doses and routes of administration on characteristics of FSH concentrations MeanS.E. in ovariectomised heifers
given a PRID ODB
No. of Pre-treatment
Mean concentration No. of hours
Maximum decline in No. of hours to
No. of hours for FSH to treatment
heifers concentrations
of FSH at nadir to reach
FSH expressed as of reach first FSH
to return to pre-treatment Ž
. Ž .
Ž .
Ž .
mg n
of FSH ngrml ngrml
FSH nadir pre-treatment values
rise following nadir concentrations
Controls
ab a
a
Ž .
0.0 3
95.916.96 102.913.1
0.0 Topical administration by intraÕaginal capsule
ab b
ad b
a a
5.0 4
110.413.45 81.511.3
24.04.2 26.66.9
30.014.9 46.516.92
ab b
a b
a a
10.0 5
97.512.70 78.610.1
24.03.8 18.96.2
33.613.3 57.615.13
Intramuscular injection in 2 ml corn oil
ab b
a b
a a
0.5 4
100.89.55 78.111.3
19.54.2 24.36.9
25.514.9 38.019.54
a b
a b
ac a
1.0 4
129.43.47 82.511.3
24.04.3 36.66.9
31.514.9 64.516.92
ab b
ac b
ad a
2.5 6
116.58.37 71.29.2
24.03.5 40.05.7
34.012.2 57.013.82
ab c
b c
b b
5.0 4
108.418.5 31.311.3
37.54.2 69.76.9
45.014.9 183.016.92
b c
bcd c
bcd b
10.0 4
75.214.11 22.313.1
34.04.9 69.58.1
104.017.2 168.019.54
a,b,c,d
Ž .
Within column, treatments with different superscripts are significantly different P - 0.05 .
Ž Ž
. increased with higher dose of ODB injected, plasma E s y0.237 q 16.109 dose y
2
Ž .
2 2
. 0.74 dose , R s 0.75; P - 0.05 but not when given topically by the intravaginal
route using the capsule. The peak plasma concentrations of E in heifers given 5- and
2
10-mg injections were similar to each other, but were higher than in heifers assigned to Ž
. all other treatments P - 0.05 . Peak concentrations of E following use of the 5- and
2
10-mg intravaginal capsules were similar to each other and to those following the 0.5 Ž
. mg injection P 0.05 , but were lower than concentrations in heifers given 1, 2.5, 5,
Ž . Ž
. and 10 mg ODB intramuscular P - 0.05
Fig. 2 . The increase in plasma concentra- tions of E in animals following the 5- and 10-mg injections were more prolonged and
2
were slower to return to pre-treatment concentrations than in animals following all other Ž
. treatments Table 1 .
3.2. Plasma concentration of FSH The effects of ODB administration on plasma concentrations of FSH are presented in
Table 2. There was a significant decline in FSH concentrations following all ODB Ž
. treatments compared with pre-treatment concentrations
P - 0.05 . The magnitude of the decline in FSH concentration was greater as blood concentration of E increased in
2
Ž .
treated animals Figs. 3 and 4 . The maximum decline in FSH concentration expressed as of pre-treatment concentrations, was significantly greater following the 5- and
10-mg injections than following all other ODB treatments. Across all treatments, both Ž .
the maximum percentage decline in FSH and the interval h to reach that decline were Ž
related to the peak plasma concentrations of E maximum decline in FSH s 11.17 q
2
Ž .
Ž .
2 2
. Ž 1.564 peak E
y 0.009 peak E , R s 0.75; P - 0.01 , hours to FSH nadir s
2 2
Ž .
Fig. 3. Effect of different doses 0, 0.5, 1, 2.5, 5, and 10 mg of ODB dissolved in 2 ml of corn oil and administered by intramuscular injection to ovariectomised heifers at the time of PRID insertion on changes
Ž .
in FSH ns 3–4 heifers per dose .
Ž Fig. 4. Effect of different doses of ODB administered either by powdered form in a gelatine capsule 5- and
. Ž
. 10-mg doses attached to PRID and two doses 0 and 0.5 mg dissolved in 2 ml of corn oil and administered
by intramuscular injection to ovariectomised heifers at the time of PRID insertion on the change in FSH in Ž
. ovariectomised heifers ns 3–4 heifers per dose .
Ž .
Ž .
2 2
. 10.628 q 1.486 hours to peak E
y 0.0282 hours to peak E , R s 0.22; P - 0.05 .
2 2
Following nadir concentrations, FSH concentration increased as E concentration de-
2
Ž Fig. 5. Effect of different doses of ODB administered either by powdered form in a gelatine capsule 10 mg
. Ž
. doses attached to PRID and two doses 1.0 and 10.0 dissolved in 2 ml of corn oil and administered by
intramuscular injection to ovariectomised heifers at the time of PRID insertion on mean plasma concentrations Ž
. Ž
. Ž
. of oestradiol E — dotted lines and FSH solid lines in ovariectomised heifers ns 4 heifers per dose .
2
clined from peak value, irrespective of treatment. However, at the higher injected doses, concentrations of FSH begin to rise again in the face of declining but still elevated
Ž .
plasma concentrations of E Fig. 5 . Concentrations of FSH following the 5- and 10-mg
2
injections took significantly longer to return to pre-treatment concentrations than in Ž
. animals assigned to all other treatments P - 0.05 .
4. Discussion
