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Effect of prolactin-release inhibition on milk production
and mammary gland involution at drying-off in cows
Ollier S, Zhao X, Lacasse P.
By: Faisal A. Alshmairy
Advisor: Dr.Moez Ayadi
Journal of Dairy Science-
Jan 2013
A dopamine agonist used to treat elevated levels of prolactin
Somatic cell count
Bovine Serum Albumin
Is the main constituent playing a buffer role in the udder
Is a component of the natural protection systems of animals, with bactericidal
& iron-binding properties
Is a Enzyme: Matrix metalloproteinase
Intra mammary Infection
Prolactin
Concepts
&
Abbreviations
Quinagolide
SCC
BSA
Citrate
Lactoferrin
MMP
IMI
(PRL)
• The lactation cycle of the dairy cow requires a dry period for optimal milk
production in the following lactation.
• Period is critical for mammary gland remodeling, the cow is highly
susceptible to new (Intra mammary Infection) IMI during the early dry period.
• After drying-off, although milk is not being removed, the mammary gland
temporarily continues to synthesize milk, which accumulates in the udder.
• The resulting increase in mammary pressure may cause leakage of milk via the
teats, allowing microorganisms to gain entry into the mammary gland.
INTRODUCTION
Beginning of Involution
low concentrations of natural protective factors: Immunoglobulins Lactoferrin
Mammary Gland Secretions Contain
Beginning of Involution
High Concentrations Of: Fat Casein Lactose Citrate
Mammary Gland Secretions Contain
-
+
Which can interfere
with the defense
capacity of the
gland & provide an
excellent medium
for bacterial growth
INTRODUCTION
• Once involution is completed, within 30 d after cessation of milking, the
mammary gland becomes much more resistant to new IMI because of a low
fluid volume in the udder and a medium unfavorable for bacterial growth.
• With increasing milk production, drying-off has become a challenging
period for the dairy cow.
• That the risk of IMI at calving increases by 77% for every 5 kg of milk
produced above 12.5 kg when milking is stopped.
• Common to dry off cows that are still producing 30 kg/d, it is important to
develop strategies that reduce milk production before drying-off & to hasten
mammary gland involution.
INTRODUCTION
Metabolic
Stress
Drastic reduction in feed
supply
in the days that precede
drying-off.
IMI
???
Intermittent Milking,
but its association with a
reduction in IMI at calving has
not been clearly proven
Method commonly used to reduce milk production is:
New
Decreasing the lactogenic
signals driving milk
production.
@agrfaisal
• Prolactin (PRL) is a hormone known to be mammogenic & lactogenic in
both monogastric & ruminant mammals.
• Inhibition of PRL secretion by quinagolide gradually decreases milk
production of cows in early lactation → suggesting also a galactopoietic
role of PRL in cows.
• This approach has never been investigated in late-lactation cows.
INTRODUCTION
1
OBJECTIVE OF THIS STUDY:
Assess the effect of inhibition of PRL release by quinagolide on milk
production just before drying-off & on concentrations of involution
markers in mammary secretions after the last milking
According to:
Milk yield, SCC, & Parity.
From 4 d before drying-off to 3 d
after (Quin)
Design of experiment
Fed ad libitum a late-lactation diet containing After drying-off, the cows were fed
a dry-period diet containing: DM:-
The feeding
Feed intake was recorded daily throughout the experiment, Cow’s BW was determined at the start & end of the experiment.
Before drying-off, the cows were milked twice daily, at 08:00 & 20:30 h, & milk yield was recorded at each milking
during the last 2 week.
Milk samples were collected at the A.M. milking on the last 5 days before drying-off (d −5 to d −1).
After the last milking, each quarter was treated with dry-cow therapy containing cloxacillin benzathine.
Mammary
secretions
60 mL - manually
1 quarter at 08:00
1d 3d 5d 7d 10d 14d
To measure SCC & determination of BSA, Lactoferrin, citrate, Na+, & K+ concentrations, and gelatinase activity.
Taken just before collection of milk and mammary secretions on
-5d -2d -1d 1d 3d 5d 7d 10d 14d
min. relative to the start of milking
All blood tubes (without additive) were left for approximately 2 h at room temperature
for clotting before centrifugation (1,900 × g, 4°C, 15 min).
Then, the serum was stored at −20°C until determination of PRL concentration.
-4 -3 -2 -1 0 1 2 3
4 day preceding drying-off 3 day after drying-off
start of drying-off
PRL concentration
@agrfaisal
Somatic cell count
(SCC) @agrfaisal
Concentration of BSA
in Milk. @agrfaisal
Concentrations of
Lactoferrin & Citrate
in Milk
Na+ & K+
Concentrations in Milk
@agrfaisal
Statistical Analysis
Data were analyzed by ANOVA using the MIXED procedure of SAS
Milk Samples
Concentrations of
Lactoferrin & Citrate Na+&K+ BSA SCC Gelatinase
Activity
RESULTS
Figure 1. Basal concentration of prolactin in the blood of cows injected twice daily with water (control,—▄—; n=8) or quinagolide
(2 mg per injection, - - □ - -; n = 8) from 4 d before drying-off (symbolized by an arrow) to 3 d after. On d −4, blood samples were taken before the first injection.
Data are presented as least squares means ± SEM, and significant differences between the treatments are indicated as follows: *P< 0.05, **P< 0.01, ***P< 0.001.
Injections
Basal concentration of prolactin in the blood
Figure 1.
Control
Treatment
Figure 2. Milk production during the last 10 d of lactation in cows injected twice daily with water (control, - ▄ -; n = 8) or quinagolide
(2 mg per injection, -- □ --; n = 8) for the last 4 d preceding drying-off.
Data are presented as least squares means ± SEM, & significant differences between the treatments are indicated as follows:*P < 0.05, ***P < 0.001.
Injections
Milk production during the last 10 d of lactation
Figure 2.
Control
Treatment
Figure 3. Somatic cell count in milk and mammary secretions of cows injected twice daily with water (control, - ▄ - n = 8)
or quinagolide (2 mg per injection,--□--; n=8) from 4d before drying-off (symbolized by an arrow) to 3d after.
On d −4, milk samples were collected before the first injection.
Data are presented as least squares means ± SEM of log10-transformed values.
Significant differences between the treatments are indicated as follows: ***P < 0.001.
Injections
Somatic cell count in milk & mammary secretions
Figure 3.
Control
Treatment
Figure 4. Concentration of BSA in milk and mammary secretions of cows injected twice daily with water (control, -▄-; n = 8) or quinagolide
(2 mg per injection, --□--; n =8) from 4 d before drying-off (symbolized by an arrow) to3 d after.
On d −4, milk samples were collected before the first injection. Data are presented as least squares means ± SEM, and significant differences
between the treatments are indicated as follows: **P < 0.01.
Injections
Concentration of BSA in milk&mammary secretions
Figure 4.
Control
Treatment
Figure 5. Citrate: Lactoferrin molar ratio in milk and mammary secretions of cows injected twice daily with water (Con. -▀- ; n = 8)
or quinagolide (2 mg per injection, --□--; n = 8) from 4 d before drying-off (symbolized by an arrow) to 3 d after.
On d −4, milk samples were collected before the first injection.
Data are presented as least squares means ± SEM of log10-transformed values.
Injections
Citrate: Lactoferrin molar ratio in milk & mammary secretions
Figure 5.
Control
Treatment
Figure 6. Matrix metalloproteinase-2 (MMP-2) level in the milk and mammary secretions of cows injected twice daily with water
(control,-▀-, solid line; n=8)or quinagolide(2mg per injection,--□--;n=8) from 4d before drying-off(symbolized by an arrow)to3d after.
On d −4, milk samples were collected before the first injection.
Data are presented as least squares means ± SEM of log10-transformed values.
Injections
Control
Treatment
Matrix metalloproteinase-2
Figure 6.
• PRL-release inhibition could be used as a tool to reduce milk production
at drying-off and to stimulate involution.
• Quinagolide caused a transient depression of feed intake as a side effect.
• The BW at the end of the experiment was not affected by treatment and
was similar to that at the start of the experiment for both groups
• In the current experiment, Researchers did not find no effects or
indicators on mastitis…
CONCLUSION
Quinagolide
@agrfaisal
Thank you
for the care & attention

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Effect of prolactin release inhibition on milk production and mammary gland involution at drying-off in cows.pptx

  • 1. Effect of prolactin-release inhibition on milk production and mammary gland involution at drying-off in cows Ollier S, Zhao X, Lacasse P. By: Faisal A. Alshmairy Advisor: Dr.Moez Ayadi Journal of Dairy Science- Jan 2013
  • 2. A dopamine agonist used to treat elevated levels of prolactin Somatic cell count Bovine Serum Albumin Is the main constituent playing a buffer role in the udder Is a component of the natural protection systems of animals, with bactericidal & iron-binding properties Is a Enzyme: Matrix metalloproteinase Intra mammary Infection Prolactin Concepts & Abbreviations Quinagolide SCC BSA Citrate Lactoferrin MMP IMI (PRL)
  • 3. • The lactation cycle of the dairy cow requires a dry period for optimal milk production in the following lactation. • Period is critical for mammary gland remodeling, the cow is highly susceptible to new (Intra mammary Infection) IMI during the early dry period. • After drying-off, although milk is not being removed, the mammary gland temporarily continues to synthesize milk, which accumulates in the udder. • The resulting increase in mammary pressure may cause leakage of milk via the teats, allowing microorganisms to gain entry into the mammary gland. INTRODUCTION
  • 4. Beginning of Involution low concentrations of natural protective factors: Immunoglobulins Lactoferrin Mammary Gland Secretions Contain Beginning of Involution High Concentrations Of: Fat Casein Lactose Citrate Mammary Gland Secretions Contain - + Which can interfere with the defense capacity of the gland & provide an excellent medium for bacterial growth INTRODUCTION
  • 5. • Once involution is completed, within 30 d after cessation of milking, the mammary gland becomes much more resistant to new IMI because of a low fluid volume in the udder and a medium unfavorable for bacterial growth. • With increasing milk production, drying-off has become a challenging period for the dairy cow. • That the risk of IMI at calving increases by 77% for every 5 kg of milk produced above 12.5 kg when milking is stopped. • Common to dry off cows that are still producing 30 kg/d, it is important to develop strategies that reduce milk production before drying-off & to hasten mammary gland involution. INTRODUCTION
  • 6. Metabolic Stress Drastic reduction in feed supply in the days that precede drying-off. IMI ??? Intermittent Milking, but its association with a reduction in IMI at calving has not been clearly proven Method commonly used to reduce milk production is: New Decreasing the lactogenic signals driving milk production. @agrfaisal
  • 7. • Prolactin (PRL) is a hormone known to be mammogenic & lactogenic in both monogastric & ruminant mammals. • Inhibition of PRL secretion by quinagolide gradually decreases milk production of cows in early lactation → suggesting also a galactopoietic role of PRL in cows. • This approach has never been investigated in late-lactation cows. INTRODUCTION 1
  • 8. OBJECTIVE OF THIS STUDY: Assess the effect of inhibition of PRL release by quinagolide on milk production just before drying-off & on concentrations of involution markers in mammary secretions after the last milking
  • 9. According to: Milk yield, SCC, & Parity. From 4 d before drying-off to 3 d after (Quin) Design of experiment
  • 10. Fed ad libitum a late-lactation diet containing After drying-off, the cows were fed a dry-period diet containing: DM:- The feeding
  • 11. Feed intake was recorded daily throughout the experiment, Cow’s BW was determined at the start & end of the experiment. Before drying-off, the cows were milked twice daily, at 08:00 & 20:30 h, & milk yield was recorded at each milking during the last 2 week. Milk samples were collected at the A.M. milking on the last 5 days before drying-off (d −5 to d −1). After the last milking, each quarter was treated with dry-cow therapy containing cloxacillin benzathine. Mammary secretions 60 mL - manually 1 quarter at 08:00 1d 3d 5d 7d 10d 14d To measure SCC & determination of BSA, Lactoferrin, citrate, Na+, & K+ concentrations, and gelatinase activity. Taken just before collection of milk and mammary secretions on -5d -2d -1d 1d 3d 5d 7d 10d 14d
  • 12. min. relative to the start of milking All blood tubes (without additive) were left for approximately 2 h at room temperature for clotting before centrifugation (1,900 × g, 4°C, 15 min). Then, the serum was stored at −20°C until determination of PRL concentration. -4 -3 -2 -1 0 1 2 3 4 day preceding drying-off 3 day after drying-off start of drying-off
  • 13. PRL concentration @agrfaisal Somatic cell count (SCC) @agrfaisal Concentration of BSA in Milk. @agrfaisal Concentrations of Lactoferrin & Citrate in Milk Na+ & K+ Concentrations in Milk @agrfaisal Statistical Analysis Data were analyzed by ANOVA using the MIXED procedure of SAS Milk Samples Concentrations of Lactoferrin & Citrate Na+&K+ BSA SCC Gelatinase Activity
  • 15. Figure 1. Basal concentration of prolactin in the blood of cows injected twice daily with water (control,—▄—; n=8) or quinagolide (2 mg per injection, - - □ - -; n = 8) from 4 d before drying-off (symbolized by an arrow) to 3 d after. On d −4, blood samples were taken before the first injection. Data are presented as least squares means ± SEM, and significant differences between the treatments are indicated as follows: *P< 0.05, **P< 0.01, ***P< 0.001. Injections Basal concentration of prolactin in the blood Figure 1. Control Treatment
  • 16. Figure 2. Milk production during the last 10 d of lactation in cows injected twice daily with water (control, - ▄ -; n = 8) or quinagolide (2 mg per injection, -- □ --; n = 8) for the last 4 d preceding drying-off. Data are presented as least squares means ± SEM, & significant differences between the treatments are indicated as follows:*P < 0.05, ***P < 0.001. Injections Milk production during the last 10 d of lactation Figure 2. Control Treatment
  • 17. Figure 3. Somatic cell count in milk and mammary secretions of cows injected twice daily with water (control, - ▄ - n = 8) or quinagolide (2 mg per injection,--□--; n=8) from 4d before drying-off (symbolized by an arrow) to 3d after. On d −4, milk samples were collected before the first injection. Data are presented as least squares means ± SEM of log10-transformed values. Significant differences between the treatments are indicated as follows: ***P < 0.001. Injections Somatic cell count in milk & mammary secretions Figure 3. Control Treatment
  • 18. Figure 4. Concentration of BSA in milk and mammary secretions of cows injected twice daily with water (control, -▄-; n = 8) or quinagolide (2 mg per injection, --□--; n =8) from 4 d before drying-off (symbolized by an arrow) to3 d after. On d −4, milk samples were collected before the first injection. Data are presented as least squares means ± SEM, and significant differences between the treatments are indicated as follows: **P < 0.01. Injections Concentration of BSA in milk&mammary secretions Figure 4. Control Treatment
  • 19. Figure 5. Citrate: Lactoferrin molar ratio in milk and mammary secretions of cows injected twice daily with water (Con. -▀- ; n = 8) or quinagolide (2 mg per injection, --□--; n = 8) from 4 d before drying-off (symbolized by an arrow) to 3 d after. On d −4, milk samples were collected before the first injection. Data are presented as least squares means ± SEM of log10-transformed values. Injections Citrate: Lactoferrin molar ratio in milk & mammary secretions Figure 5. Control Treatment
  • 20. Figure 6. Matrix metalloproteinase-2 (MMP-2) level in the milk and mammary secretions of cows injected twice daily with water (control,-▀-, solid line; n=8)or quinagolide(2mg per injection,--□--;n=8) from 4d before drying-off(symbolized by an arrow)to3d after. On d −4, milk samples were collected before the first injection. Data are presented as least squares means ± SEM of log10-transformed values. Injections Control Treatment Matrix metalloproteinase-2 Figure 6.
  • 21. • PRL-release inhibition could be used as a tool to reduce milk production at drying-off and to stimulate involution. • Quinagolide caused a transient depression of feed intake as a side effect. • The BW at the end of the experiment was not affected by treatment and was similar to that at the start of the experiment for both groups • In the current experiment, Researchers did not find no effects or indicators on mastitis… CONCLUSION