Veterinary Quarterly

ISSN: 0165-2176 (Print) 1875-5941 (Online) Journal homepage: https://www.tandfonline.com/loi/tveq20

Growth and growth hormone in the dog

R.C. Nap , J.A. Mol & H.A.W. Hazewinkel

To cite this article: R.C. Nap , J.A. Mol & H.A.W. Hazewinkel (1994) Growth and growth hormone
in the dog, Veterinary Quarterly, 16:sup1, 31-32, DOI: 10.1080/01652176.1994.9694473

To link to this article: https://doi.org/10.1080/01652176.1994.9694473

Copyright Taylor and Francis Group, LLC

Published online: 01 Nov 2011.

Submit your article to this journal

Article views: 363

Citing articles: 2 View citing articles

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=tveq20
 ilWOIKreZ.z.MIntrP
MEDICINE & SURGERY
8. Squire RA, Bush M, Melby EC, Nee ley LM, and Yarbrough B. Clinical
and pathologic study of canine lymphoma: clinical staging, cell classifi-
cation, and therapy. J Natl Cancer Inst 1973; 51: 565-74.
9. Greenlee PG, Filippa DA, Quimby FW, Patnaik AK, Calvano SE, Matus
RE, Kimmel M, Hurvitz Al, and Lieberman PH. Lymphomas in dogs. A
morphologic, immunologic, and clinical study. Cancer 1990; 66: 480-
90.
10. Teske E, Wisman P, Moore PF, and Van Heerde P. Histological classifi-
cation and immunophenotyping of canine non-Hodgkin's lymphomas.
Unexpected high frequency of T-cell lymphomas with B-cell morpho-
logy. Exp Hematol, accepted for publication.
11. Hardy WD, and Old LI L-asparaginase in the treatment of neoplastic
diseases of the dog, cat and cow. Recent Results in Cancer Res 1970; 33:
131-9.
12. Postorino NC, Susaneck SJ, Withrow SI, Macy DW, and Harris C.
Single agent therapy with Adriamycin for canine lymphosarcoma. J Am
Anim Hosp Assoc 1989; 25: 221-5.
13. Teske E, Rutteman GR, Van Heerde P, and Misdorp W. Polyethylene
glycol-L-asparaginase in canine non-Hodgkin's lymphoma. Eur J
Cancer 1990; 26: 891-5.
14. MacEwen EG, Rosenthal RC, Fox LE, Loar AS, and Kurzman ID.
Evaluation of L-asparaginase: polyethylene glycol conjugate versus na-
tive L-asparaginase combined with chemotherapy. A randomized dou-
ble-blind study in canine lymphoma. J Vet Int Med 1992; 6: 230-4.
15. Carter RF, Harris CK, Withrow SJ, Valli VEO, and Susaneck SI.
Chemotherapy of canine lymphoma with histopathological correlation:
doxorubicin alone compared to COP as first treatment regimen. J Am
Anim Hosp Assoc 1987; 23: 587-96.
GROWTH AND GROWTH HORMONE
IN THE DOG
1
P.C. Nap, J.A. Mol, and H.A.W. Hazewinker
Dogs present a uniquely wide diversity in body size and
body weight. Adult dogs at the opposite ends of the size scale
differ in weight by a factor of nearly 100. Body shape and
proportions range widely. In the 1940's it was proposed that
the characteristic structural and functional peculiarities
found among breeds might be due to genetic variations
which bring about alterations in endocrine function. It was
even proposed that giant breed dogs such as the Great Dane
and the Saint Bernard have features similar to those seen in
acromegaly and gigantism (16). Longitudinal growth is pri-
marily the result of chondrocyte cell mitosis, cell enlarge-
ment, and matrix growth in the physis and occurs within the
genetically determined time frame and is influenced by a
large variety of environmental factors. The rate and extent of
longitudinal bone growth is regulated by complex interac-
tions of biochemical factors, systemic endocrine factors, and
local para- or autocrine factors that act on chondrocytes and
matrix in the growth plate (18). The time frame and sequence
for growth plate closure are gene related, but environmental
influences during health and disea-se Will modify both within
the pre-set genotypical limits (13). GH also influences the in-
crease in body weight i.e., body mass by the effects on fat-
and muscle cell growth and metabolism. These effects will
not be discussed in detail in this paper.
1 Department of Clinical Scienes of Companion Animals, Faculty of Veterinaly medi-
cine, Utrecht UniversBv, P.O. Box 80.154, NL-3508 TD Utrecht, the Netherlands
31S THE V E T E R I N A R Y Q U A R T E R L Y , V O L .
16. Teske E, Van Heerde P, Rutteman GR, Kurzman I, Moore PF, and
MacEwen EG. Prognostic factors in canine non-Hodgkin's lymphomas.
A prospective study in 138 dogs. J Am Vet Med Assoc, accepted for pu-
blication.
17. MacEwen EG, Hayes AA, Matus RE, and Kurzman I. Evaluation of
some prognostic factors for advanced multicentric lymphosarcoma in
the dog. 147 cases (1978-1981). J Am Vet Med Assoc 1987; 190: 564-8.
18. Keller ET, MacEwen EG, Rosenthal RC, Helfland SC, and Fox LE.
Evaluation of prognostic factors and sequential combination chemothe-
rapy with doxorubicin for canine lymphoma. J Vet Int Med, 1993; 7:
289-95.
19. Teske E, Besselink CMLT, Blankenstein MA, Rutteman GR, and
Misdorp W. The occurrence of estrogen and progestin receptors and
anti-estrogen binding sites (AEBS) in canine non-Hodgkin's lympho-
mas. Anticancer Res 1987; 7: 857-60.
20. Vicini DS, Oglivie GK, Katzenellenbogen I, and Carlson K.
Measurement of estrogen receptors in normal and neoplastic lymph
node tissue from dogs. Am J Vet Res 1991; 52: 2055-9.
21. Cotter SM. Treatment of lymphoma and leukemia with cyclophospha-
mide, vincristine, and prednisone: I. Treatment of dogs. J Am Anim
Hosp Assoc 1983; 19: 159-65.
22. MacEwen EG, Brown NO, Patnaik AK, Hayes AA, and Passe S. Cyclic
combination chemotherapy of canine lymphosarcoma. J Am Vet Med
Assoc 1981; 178: 1178-81.
23. Braylan RC. Flow-cytometric DNA analysis in the diagnosis and pro-
gnosis of lymphoma. Am I Clin Pathol 1993; 99: 374-80.
24. Teske E, Rutteman GR, Kuipers-Dijkshoorn NJ, Van Dierendonck JH,
Van Heerde P, and Cornell sse CJ. DNA ploidy and cell kinetic characteris-
tics in canine non-Hodgkin's lymphoma. Exp Hematol 1993; 21: 579-84.
W".
The most important endogenous regulator of body growth is
growth hormone (GH) which is secreted in the pituitary
gland under the influence of hypothalamic factors (somato-
crinin and somatostatin). The GH secretion in the dog is pul-
satile with basal levels in adult dogs in the 1 to 4 p.g/1 range,
whereas spontaneous peaks may reach 15 to 20 Rg/l. The du-
ration of GH pulses in the dog is approximately 1 hour and
the pulse interval is 4 - 6 hours (2, 6, 20).
The effects of GH on the growth plate are both direct and in-
direct, the latter via the production of insulin-like growth
factors (IGFs) in the liver and in the target organs (12, 14).
The primary effect of GH on the growth plate is the stimula-
tion of chondrocyte differentiation. IGF-I as present in
plasma is mainly produced in the liver, and more than 95% of
this circulating IGF-I is tightly bound to plasma proteins and
does not contribute to IGF bioactivity. The main effect of
IGF-I on the growth-plate chondrocytes is cell proliferation.
It is now known that differences in body size and body
weight in men, mice, rat and pigs can be correlated to diffe-
rences in IGF-I and to differences in thyroxine levels
(7,15,17,22). Because breed related differences for adult
body size among dogs are correlated to differences in plasma
IGF-I levels but not to GH secretory capacity (5), the
questions arises how plasma IGF-I levels during growth are
related to adult body size. Only limited data are available
from longitudinal studies on the plasma GH and IGF-I con-
16, SUPPLEMENT 1 , APRIL 1994
 g;&,' eit'M
- MEDICINE & SURGERY
centration during growth in small and giant breed dogs (1,2).
In man, basal plasma GH concentrations increase with age
from birth onward to reach a maximum at late adolescence,
followed by a decline during adulthood (3,21).
We studied miniature poodles and Great Danes raised under
standardized conditions from weaning until 6 months of age.
Diets were formulated to meet the NRC recommendations
(11) for all macronutrients.
Longitudinal growth was studied by measuring the length of
the radius and ulna on a lateral radiograph (19) and secondly
by measuring physeal growth in histological sections of co-
stal growth plates (8). Blood samples for GH and IGF-I were
collected at fixed intervals in both breeds. GH was measured
by a specific homologous radioimmunoassay (4) and plasma
IGF-I concentrations were measured by radioimmunoassay
of extracted plasma as described previously (9,10).
Antiserum to human IGF-I (Nr. UBK487) was a generous
gift from Drs Underwood and VanWyk, University of North
Carolina, as distributed by the hormone distribution program
of the NIDDK.
In both groups physical examination revealed no abnormali-
ties and the results of routine laboratory studies were within
reference ranges for growing dogs. Body weight at the end of
the experiment was 5.0 and 35.0 kg in the poodles and the
Great Danes, respectively. Differences between breeds were
significant throughout the experiment.
In the poodles the mean basal plasma GH levels did not
change significantly with time and values were within the
normal range for adult dogs. In the Great Danes the mean GH
values decreased significantly between 9 and 27 weeks of
age. Differences between mean basal plasma GII concentra-
tions for the two groups were significant except at 27 weeks
of age. "14
Between 13 and 27 weeks of age the mean IGF-I concentra-
tions in poodles decreased, whereas the IGF-I plasma values
in the Great Danes was not correlated with time in experi-
ment. In the poodles a significant correlation was found be-
tween mean IGF-I concentration and age. In neither of the
two groups was there a correlation between plasma basal GH
and plasma IGF-I concentrations throughout the study.
It is concluded that the high plasma GH concentrations in
young Great Danes may indicate a period of physiologic gi-
gantism during early postnatal growth.
REFERENCES
I. Blum JW, Zentek J und Meyer H. Untersuchungen zum Einfluss einer
unterschiedlichen Energie Versorgung auf Wachtumintensität und
Skelettentwicklung bci wachsender Doggen. 2. Mitteilung: Einfluss auf
den insulinänlichen Wachtumsfaktor I und auf Schilddriisenhormone.
Zentralblatt für Veterinärmedizin 1992; Reihe A 39: 568-74.
2. Chakraborty PK, Stewart AP, and Seager SWJ. Relationship of growth
and serum growth hormone concentration in the prepubertal labrador
bitch. Lab Anim Sci 1983; 33: 51-5.
3. Daughaday WH. Growth hormone and the somatomedins. In: Endocrine
32S THE VETERINARY QUARTERLY, V O L .
control of growth, Daughaday WH ed. New York USA: Elsevier, 1981;
1-24.
4. Eigenmann JE, and Eigenmann RY. Radioimmunoassay of canine
growth hormone. Acta Endocrinol 1981; 98: 514-20.
5. Eigenmann JE, Patterson DF, and Froesch ER. Body size parallels insu-
lin-like growth factor I levels but not growth hormone secretory capa-
city. Acta Endocrinol (Copenh) 1984; 106: 448-53.
6. French MB, Viatkus P, Cukerman E, Sirek A, and Sirek OV.
Secretory pattern of canine growth hormone. Am J Physiol 1987; 252
(Endocrinol Metab 15): E268-72.
7. Glasscock GF, Hein AN, Miller JA, Hintz RL, and Rosenfeld RG.
Effects of continous infusion of insulin-like growth factor I and II, alone
and in combination with thyroxine or growth hormone, on the neonatal
hypophysectomized rat. Endocrinol 1992; 130: 203-10
8. Goedegebuure SA, and Hazewinkel HAW. Morphological findings in
young dogs chronically fed a diet containing excess calcium. Vet Pathol
1986; 23: 594-605.
9. Nap RC. Nutritional influences on growth and skeletal development in
the dog. Thesis Utrecht June 1993 (ISBN 90-393-0256-1).
10. Nap RC, Mol JA, and Hazewinkel HAW. Age-related plasma concen-
trations of growth hormone (GH) and insulin-like growth factor I (IGF-
I) in Great Dane pups fed different dietary levels of protein. Dom Anim
Endocrinol 1993; 10: 237-47.
11. National Research Council. Nutrient Requirements of Dogs. National
Academy of Sciences, National Academy Press, Washington DC USA
1974: 1-79.
12. Nilsson A, lsgaard J, Lindahl A, Dahlstrom A, Skottner A, and lsaksson
OGP. Regulation by growth hormone of number of chondrocytes contai-
ning IGF-I in rat growth plate. Science 1986; 233: 571-4.
13. Ogden JA, and Rosenberg LC. Defining the growth plate. In: Behavior
of the growth plate. Uhthoff HK and Wiley 1.1 eds. New York USA:
Raven Press, 1988: 1-14. Siddiqui RA, Blair HT, McCutcheon SN,
Mackenzie DDS, Gluckman PD, and Breier BH. Developmental pat-
terns of plasma insulin-like growth factor-I (IGF-1) and body growth in
mice from lines divergently selected on the basis of plasma IGF-I. J
Endocrino1,1990; 124: 151-8.
15. Schlechter NL, Russel SM, Spencer EM, and Nicoll CS .
Evidence suggesting that the direct growth-promoting effect of growth
hormone on cartilage in vivo is mediated by local production of somato-
medin (IGF). Proc Natl Acad Sci USA 1986; 83: 7932-4.
16. Stockard CR. The genetic and endocrinic basis for differences in form
and behavior.
,
In: The American Anatomic Memoirs Number 19, The
Wistar Institute of Anatomy and Biology, Philadelphia, PA, USA, 1941:
1-42.
17. Tixier-Boichard M, Huybrechts LM, Decuypere E, Kan ER,
Momvoisin J-L, Coquerelle G, Charrier J, and Simon J. Effects of insu-
lin-like growth factor-I (IGF-1) and dietary tri-iodothyronine (T3 ) sup-
plementation on growth, body composition and plasma hormone levels
in sex-linked dwarf mutant and normal chickens. J Endocrinol 1992;
133: 101-10.
18. Trippel SB. Growth plate regulation: the somatomedins. Pathol and
Immunopathol Res 1988; 7: 43-7.
19. Voorhout G, and Hazewinkel HAW. Radiographic studies of the skele-
tal development in Great Danes on different calcium intakes. Vet Radiol
1987; 28: 152-7.
20. Watson ADJ, Rutteman GR, Rijnberk A, and Mol JA. Effect of somato-
statin analogue SMS 201-995 and antiprogestin agent RU 486 in canine
acromegaly. Front Horm Res 1987; 17: 193-8.
21. Zadik Z, Chalew SA, McCarter RJ, Meistas M, and Kowarski AA. The
influence of age on the 24-hour integrated concentration of growth hor-
mone in normal individuals. J Clin Endocrinol Metab 1985; 60: 513-6.
22. Zenobi PD, Guler H-P, Zapf J, and Froesch ER. Insulin-like growth fac-
tors in the Gottinger miniature-pig. Acta Endocrinol (Copenh) 1988;
117: 343-52.
16 , SUPPLEMENT 1 , A P R I L 1 9 9 4