Livestock Production Science 68 2001 79–86 www.elsevier.com locate livprodsci
Effects of recombinant ovine placental lactogen and recombinant ovine growth hormone on growth of lambs and
q
milk production of ewes
a a
b c ,
Haim Leibovich , Arieh Gertler , Fuller Bazer , Elisha Gootwine
a
Institute of Biochemistry , Food Science and Nutrition, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel
b
Center for Animal Biotechnology and Genomics , Institute of Biosciences and Technology,
Texas A M University System Health Science Center, College Station, TX 77843-2471, USA
c
Institute of Animal Science , ARO, The Volcani Center, P.O. Box 6, 50250 Bet Dagan, Israel
Received 12 August 1999; received in revised form 20 December 1999; accepted 20 May 2000
Abstract
The somatogenic and galactopoietic effects of recombinant ovine placental lactogen oPL were compared with the effects of recombinant ovine growth hormone oGH in post-weaned growing lambs and in lactating ewes. In two experiments that
each lasted 35 days, 2-month-old lambs were given daily subcutaneous injections 0.1 mg kg live weight of oPL or oGH, and their daily growth rates were compared with those of non-treated control lambs. Ovine GH and oPL had similar
profound P , 0.01 growth-stimulating effects, enhancing lamb growth by 10 to 25. In two other experiments, lactating
ewes were injected with oGH or oPL 0.1 mg kg live weight day for 14 days in mid-lactation. Treatment with oGH increased P
, 0.001 daily milk production by up to 55 over control ewes. Ovine PL increased P , 0.01 milk production by up to 25. In all experiments, treatment of lambs or lactating ewes with oGH, but not with oPL increased P
, 0.05 serum insulin-like growth factor-I concentrations. It is concluded that oPL and oGH have similar somatogenic effects in
lambs. Both hormones exhibited galactopoietic effects, but oGH was considerably more potent than oPL.
2001 Elsevier Science B.V. All rights reserved.
Keywords : Placental lactogen; Growth hormone; Growth; Milk production; Sheep; IGF-I
1. Introduction ruminants synthesize and secrete unique proteins that
belong to the growth hormone prolactin GH PRL Similar to other mammalian species, placentae of
family and are called placental lactogens PLs Byatt et al., 1992b. Ovine o Martal and Djiane,
1975; Warren et al., 1990 and bovine b Murthy et
q
Contribution from the Agricultural Research Organization,
al., 1982 PLs are 22 to 23 kDa proteins which are,
The Volcani Center, Bet Dagan, Israel. No. 337 99, 1999 series.
based on structural analysis and gene mapping, more
Corresponding author. Tel.: 1 972-3-9683-752; fax: 1 972-8-
closely related to their respective PRL than GH
475-075. E-mail address
: gootwineagri.gov.il E. Gootwine.
Byatt et al., 1992b; Gootwine and Yossefi, 1998.
0301-6226 01 – see front matter
2001 Elsevier Science B.V. All rights reserved. P I I : S 0 3 0 1 - 6 2 2 6 0 0 0 0 2 1 1 - 6
80 H
. Leibovich et al. Livestock Production Science 68 2001 79 –86
One unique property of ruminant PL which was 2. Materials and methods
observed early on is their ability to bind to both PRL and GH receptors, including receptors for human
The Volcani Center Animal Care Committee ap- hGH Forsyth, 1986; Anthony et al., 1995a,b. This
proved the experimental protocols used in this observation suggested that GH and PL may have
research. similar biological activities. However, attempts to
prove this hypothesis using in vitro experimental 2.1. Materials
systems yielded contradictory results depending on whether a homologous or a heterologous model
Recombinant oPL and oGH were prepared as system was chosen. Both bPL and oPL were potent
described previously Sakal et al., 1997. Human agonists in FDC-11P cells stably transfected with
insulin-like growth factor-I IGF-I and antiserum human or rabbit GH receptors, and their activities
against IGF-I were obtained from Fugisawa Pharma- were comparable with those of hGH and oGH,
ceutical Osaka, Japan. Antiserum against oGH was respectively Helman et al., 1997, 1998; Sakal et al.,
obtained from the National Hormone Pituitary Pro- 1997. In contrast, in ‘‘293’’ cells transiently trans-
gram University of Maryland School of Medicine, fected with oGH or hGH receptors, ruminant PL
MD, USA. Goat anti-rabbit IgG and normal rabbit were active only in cells transfected with hGH
serum were purchased from Bio-Makor Rehovot, receptors Herman et al., 1999. In cells transfected
Israel. Antiserum against oPL was prepared in
125
with oGH receptors, only oGH acted as an agonist, rabbits in our laboratory. Carrier-free Na[
I] was whereas ruminant PL, despite their ability to bind to
purchased from New England Nuclear Corp. Bos- those
receptors, exhibited
antagonistic activity.
ton, MA, USA. Therefore, it was concluded that ruminant PL can
bind to, but not homodimerize, oGH receptors 2.2. Animals, housing and feeding
Herman et al., 1999. Results from in vivo comparisons of PL and GH
The experiments were conducted with the Kat- bioactivities are also inconsistent. Whereas adminis-
zenelbugen dairy flock, which includes 600 Assaf tration of both bPL or bGH increased growth and
breeding ewes, at Moshav Talmai Elazer. This flock milk production in rats, only bGH affected milk
is kept indoors all year round and the ewes are fed yield in dairy cows Byatt et al., 1992a. Further-
according to Israeli Ministry of Agriculture recom- more, oPL failed to show GH-like galactopoietic
mendations Landau and Leibovich, 1992. All the properties when injected into ewes Min et al.,
lambs of this flock are routinely separated from their 1995. Bovine GH, but not bPL, had stimulatory
dams on the day of lambing, and are moved to an effects on lamb growth rate in one study McLaug-
artificial rearing unit where they receive a commer- hlin et al., 1993 while, in another study, administra-
cial milk replacer ad libitum until weaning at approx- tion of oPL to growing lambs significantly increased
imately 25 days of age. Following weaning, lambs their growth rate, whereas bGH did not Min et al.,
have free access to concentrates, hay and water. 1996. This latter result contradicts several other
Ewes are milked at 08:00 and 16:00 daily from the studies where bGH had a growth-promoting effect in
day of lambing until milk yield decreases to approxi- lambs Wagner and Veenhuizen, 1978; Rosemberg et
mately 0.5 l day. al., 1989.
Recombinant oPL Colosi et al., 1989; Sakal et al., 2.3. Growth-promoting effects following
1997 and bPL Krivi et al., 1989 have been administration of oPL and oGH
prepared, and were produced in our laboratory Gertler et al., 1992; Sakal et al., 1997 in amounts
Sixty male lambs born in February 1995 and 36 sufficient for in vivo studies with a large number of
male lambs born in March 1997 were used in two animals. Therefore, the present study compared the
experiments. In each experiment, 2-month-old lambs effects of oPL and oGH in a homologous in vivo
were allocated to experimental groups according to system, using two experimental models: growing
their weight, post-weaning growth rate, litter size and lambs and lactating ewes.
age. The lambs were fed concentrates 16 crude
H . Leibovich et al. Livestock Production Science 68 2001 79 –86
81
protein ad libitum and hay at 0.1 kg head day. infrared analyzer Milkoscan 134; N. Foss Electric,
Lambs were treated daily at 10:00 for 35 days with Hillerod, Denmark.
saline solution containing 0.1 mg kg body weight of oPL oPL group or oGH oGH group, or received
2.6. Radioimmunoassays saline only control group. Lambs were weighed at
the beginning of the injection period and once a Serum concentrations of oGH Peri et al., 1993,
week thereafter until the end of the injection period. IGF-I Breier et al., 1991 and oPL Kann, 1971
Group feed consumption was monitored daily. Blood were determined as described previously. Iodination
samples for hormone assays were collected from the of oGH and oPL was performed as described previ-
jugular vein on the morning time of day 34 of the ously Gertler et al., 1984. The inter- and intra-
injections, prior to the daily hormone administration, assay coefficients of variation were 12.4 and 8.7
to obtain serum, which was stored at 2 208C until
for IGF-I, 10.4 and 6.2 for oGH, and 8.8 and assayed.
6.4 for oPL, respectively. 2.7. Data analyses
2.4. Galactopoietic effects following administration of oPL and oGH
Lamb growth rates were calculated by fitting linear regressions to the body weight measurements
Forty-five multiparous ewes that lambed during 2 and then subjecting them to analysis of variance. The
weeks in October 1997 and 143 multiparous ewes model included the main fixed effects of experiment
that lambed during 2 weeks in October 1998 were 1, 2 and experimental group oPL, oGH and
used in two experiments to determine daily milk control. Lamb weight at the beginning of the
production, recorded weekly from lambing. In each experiment was used as a covariate. Results from
