Biochemical Society Transactions (1997) 25 4538
84 Regulation of growth hormone secretion in lactating sheep
alucose
ANNE FAULKNER and PAMELA A MARTIN
Hannah Research Institute. AYR KA6 5HL UK
Elevated growth hormone concentrations with their associated
vascular effects and insulin resistance are characteristic of the
etiology of diabetes [1,2,3]. Part of the problem appears to be an
abnormal regulation of growth hormone secretion from the anterior
pituitary with the normal inhibitory action of metabolic events such
as hyperglycaemia no longer being effective [4,5]. The lactating
ruminant also has elevated plasma growth hormone concentrations
and exhibits insulin resistance [6 - 91. Therefore, studies on the
regulation of growth hormone secretion in lactating animals may
also elucidate the defects in regulation associated with the diabetic
condition. Sheep exhibit episodic release of growth hormone with
ewes probably having a less pulsatile profile than their male
counterparts [ 10 - 121 In this they may resemble female rats which
show pulsatile release of growth hormone but also appear to have
a sustained secretion between the episodic events [13]. We have
studied the effects of hyperglycaemia and hyperinsulinaemia on
growth hormone secretion in fed and starved, lactating and control,
ewes, during the midmorning period when pulsatile release was
minimal.
Sheep were infused via a jugular catheter with glucose
(25pmolkglmin) or saline for 30 min. AAer 15 min GLP
(3.3ngkglmin) or saline was also infused. The glucose infusions
raised plasma glucose concentrations by a mean value of 1.3
wmol/ml. Serum insulin concentrations were also elevated during
glucose infusion by a mean value of 0.5 nglml and were further
increased by a mean value of 0.4 ng/ml when the insulinotropic
agent, GLP, was infused simultaneously. GLP infusion with saline
resulted in no sigrulicant rise in serum insulin concentrations. Mean
plasma growth hormone concentrations during these infusions are
shown in Fig 1. No significant changes were observed in control
ewes during any of the inhsions (preinfusion 1.31 0.36, 1.52 f
0.44, 1.44* 0.28 to 1.26 f 0.3 1, 1.50 0.33, 1.71 f 0.77 ng/ml for
glucose + GLP in fed, glucose +GLP in starved, and glucose alone
in fed ewes respectively by the end of infusions). Lactating animals
demonstrated sigrulicant(p<O.Ol) increases during glucose i n h i o n
(preinfusion 14.90 f 5.59 to 20.5 f 10.8 nglml) and these were
further significantly (p<0.05) elevated when GLP was infused
simultaneously (preinfusion 8.29 1.50 to 18.9 f 6.0 nglml).
Lactating ewes which had feed withdrawn for 24 h had an even
greater response (p<0.04 compared to fed equivalent) to glucose
and GLP inhsion (preinhsion 10.07 f 2.89 to 29.79 10.3 nglml).
That the effects of GLP were via increased insulin secretion is
indicated by the fact that GLP inhsions at euglycaemia had no
sigrulicant effect on growth hormone concentrations in either group
(GLP is only insulinotropic under hyperglycaemic conditions).
The lactating (but not the control) ewes show an abnormal
pattern of regulation of growth hormone secretion which is similar
to that described for the newly-diagnosed insulin-dependent diabetic
patient but not the insulin-controlled patient [141. Hyperglycaemia,
which normally inhibits growth hormone secretion, stimulated
release of growth hormone and hyperinsulinaemia also stimulated
via a mechanism not involving hypoglycaemia [4,5]. It is interesting
t o speculate that the lactating ruminant exhibits some of the
metabolic disorders characteristic of the insulin-dependent diabetic
patient but in a physiological rather than pathological situation.
Studies on lactating ruminants may help to elucidate that the factors
responsible for this aspect of diabetes.
*
*
Abbreviations used:
GLP Glucagon-like polypeptide - 1 (7-36)amide
a Iuc os e
0
c
E
L
0
r
qyq
GLP
30
20
10
rlMMMh-rrrlMMMMtl
0
30
60
90
120 150 180
time (min)
Figure 1 Changes in the concentrations of plasma growth hormone
in response to infbsions of GLP and/or glucose.
Values are the means of six lactating (A)and six control (0)ewes.
Glucose (25 lmoVkg/min) was inhsed for 30 min and GLP
(3.3ngkglmin) for 15 min as shown by the horizontal bars. Fed
sheep were 3h post feeding. Starved ewes were 24 h post feeding.
Acknowledgements
The authors thank SOAEFD for financial support.
1. Orskov, H. ( 1996)Metaholism 45,9 1-95
2. Giustina, A & Wehrenberg, W.B. (1994) Trends Endocrinol.Metah.
5,73-78
3. Schaper, N.C. (1990)Acra Endocrinologia 122,7-12
4. Sharp, P.S., Mohan, V., Maneschi, F., Vitelli, F., Cloke, H.R., Burrin,
J.M. & Kohner, E.M. (1987)Metaholism36,71-75
5 . Press, M., Caproi, S . , Tamborlane, W.V., Bhushan, R., Thorner, M.,
Vale, W., hvier, J. & Sherwin, R.S. (1992) Diabetes 41, 17-21
6. Bassett, J.M. (1989)J Agri. Sci. 113, 173-182
7. Vernon, R.G., Clegg, R.A. & Flint, D.J. (1981 ) Biochem. J 200,3073 14
8 . Vernon, R.G., Faulkner, A,, Hay, W.W., Calvert, D.T. 6( Flint D.J.
(1990)Biochem. J. 270,783-786
9. Faulkner, A. & Pollock, H.T. (1990)J Endocrmol. 124,59-66
10. Estienne, M.J., Schillo, K.K., Green, M.A. & Boling, J.A. (1989)
Endocrinology 125,85-91
1 1. Frohman, L.A., Downs, T.R., Clarke, I.J. & Thomas, G.B. (1 990) J
Clin. Invest. 86, 17-24
12. McLRod, K.R, Harmon,D.L., Schilli, K.K., Hileman, S.M. & Mitchell,
G.E. (1995) Comp. Biochem. Physiol. 112B, 523-533
13. Shapiro,B.H.,Agrawal, A.K. & Pampori, N.A. (1995)Int. .
I
Biochem.
Cell Biol. 27,9-20
14. Imaki, T., Shibasaki, T., Masuda, A,, Hotta, M., Yamauchi, N.,
Demura, H., Shizume,K., Wakabayashi, I. & Ling, N. (1986)
Endocrinology 118,2390-2394