Perinatal adrenocortical function in relation to the growth rate

and immunoglobulin acquisition of goat kids

J.C. Chen, C.J. Chang*, H.C. Peh, S.L. Lee

Department of Animal Science, National Chung Hsing University, 250 Kao-Kung Road, Taichung, Taiwan

Accepted 25 February 1999

Abstract

Serum cortisol concentration at birth can re¯ect the prenatal adrenocortical function of young animals. Its relation with the

growth rate and serum g-globulin levels during the ®rst 5 days of post-natal life was studied in full-term and eutocial goat kids.

Two groups of kids born with high (n � 14, 10.59 � 0.43 mg/dl) or low (n � 15, 5.09 � 0.28 mg/dl) serum cortisol levels had

similar (p> 0.05) mean birth weight, serum glucose and g-globulin concentrations at birth. Post-natal pro®les of serum cortisol

for kids of both groups declined to a similar (p > 0.05) level by 2 days of age. The ACTH responsiveness of serum cortisol at 5

days of age was not different (p > 0.05) between groups. The kids with higher serum cortisol levels at birth gained about 33%

more weight (p < 0.05) during the 5-day period than those with lower serum cortisol levels. Serum glucose levels after birth

remained normal at all time intervals measured and were higher (p < 0.05) for kids born with high serum cortisol levels. The

peak serum g-globulin level reached at about 18 h after the ®rst colostrum feeding was greater in kids of `high' cortisol group,

and a consistently greater level of serum g-globulin was maintained throughout the study compared to the kids of the `low'

cortisol group. The results suggest that there does not appear to be a relationship between serum cortisol levels at birth and

birth weight or post-natal adrenocortical function of normal kids. High serum cortisol levels at birth are desirable for growth

and immunoglobulin acquisition of neonatal kids. The possible mechanisms were discussed. # 1999 Elsevier Science B.V.

All rights reserved.

Keywords: Serum cortisol; Adrenocortical function; Serum g-globulin; Growth rate; Goat kids

1. Introduction

There have been abundant reports documenting the

increase of fetal cortisol concentration during late

gestation in sheep (Bassett and Thorburn, 1969;

Magyar et al., 1980; McMillen et al., 1987, 1989),

calves (Stott and Reinhard, 1978; Stott, 1980; Night-

engale and Stott, 1981), pigs (Randall, 1983; Spencer

et al., 1989), goats (Currie and Thorburn, 1977),

camels (Agarwal et al., 1992) and rats (Nagaya and

Widmaier, 1993). The increased activity of the fetal

hypothalamus±pituitary±adrenal (HPA) axis during

this stage is responsible for this increase through

various mechanisms including increased adrenocorti-

cotropic hormone (ACTH) secretion, increased adre-

nal sensitivity to ACTH, increased ACTH release in

response to corticotropin releasing factor (CRF), as

well as increased adrenal size and transcortin concen-

Small Ruminant Research 33 (1999) 255±262

*Corresponding author. Tel.: +886-4-481-2446; fax: +886-4-

286-0265; e-mail: crchang@mail.nchu.edu.tw

0921-4488/99/$ ± see front matter # 1999 Elsevier Science B.V. All rights reserved.

PII: S 0 9 2 1 - 4 4 8 8 ( 9 9 ) 0 0 0 2 9 - 2

tration (Rose et al., 1982; Hargrave and Rose, 1986;

Wood, 1991). There is good evidence that this increase

is also involved in fetal maturation and initiation of the

onset of parturition (Nathanielsz, 1976).

It has long been discovered that glucocorticoids

play a role in the intestinal epithelium absorption of

immunoglobulins (Ig) and gut closure to macromole-

cular absorption (Halliday, 1959). They produce an

early cessation in Ig absorption in rats by increasing

the rate by which absorptive epithelial cells in the

intestine are replaced by mature cells (Clark, 1971;

Patt and Eberhart, 1974). Piglets from sows treated

with metyrapone or ACTH absorbed signi®cantly

more IgG from colostrum than control piglets (Bate

and Hacker, 1985). Conversely, lambs given metyr-

apone treatment at birth had the lowest Ig concentra-

tion compared to ACTH or control lambs; and

precocious closure to Ig absorption had occurred by

20 h of life (Hough et al., 1990). It was also observed

that of both ingestive and aggressive behavior of

piglets was in¯uenced by the pre-natal stimulation

of the sows' adrenal gland activity (Bate, 1991);

therefore, elevation of periparturient plasma ACTH

and cortisol might be important for neonates to survive

during the pre-weaning age. On the other hand, due to

the catabolic effects of glucocorticoids in the muscle,

signi®cant negative correlations were found between

birth weight and plasma cortisol in early neonatal life

of female pigs (Klemcke et al., 1993). The growth rate

of young female rats was demonstrated to be inversely

correlated with plasma glucocorticoid levels (Sillence

and Rodway, 1987; Sillence et al., 1992). To further

investigate how the adrenocortical function during

perinatal stage of kids might affect their Ig absorption

and growth rate, the current study used two groups of

kids born with high or low serum cortisol levels to

compare their post-natal serum g-globulin levels dur-

ing the ®rst 5 days of age and growth performance as

well as the responsiveness to ACTH.

2. Material and methods

2.1. Environment, animals and sample collection

Seventeen pregnant Nubian does in their 2±3 pari-

ties kidded during February 1996 with a mean (� SD)

BW of 48.5 � 4.5 kg after parturition were used. They

were selected from about 200 does from two farms in

Taiwan located within 22±248N, 1208E; with 15±188Caverage ambient temperature during the experimental

period. They were maintained in high rise slatted pens

since breeding under the in¯uence of natural day light

and temperature. All does were fed maize grain and

SBM-based pelleted concentrate and suf®cient pan-

gola hay or pangola silage according to suppliers.

Compositions of feeds are described in a previous

report (Chen et al., 1999). They received their daily

meal to meet the estimated gestation, lactation and

BW maintenance requirements (NRC, 1981) as morn-

ing and evening meals and water was available all the

time. Kidding was supervised by an experienced

herdsman. Kids used in this experiment were full-

term kids that did not require hand or mechanical

assistance at parturition. The kids were separated from

their dams at birth, weighed prior to the ®rst feeding,

and placed in a pen regulated at 25 � 28C with a heater

and wind shield. Kids were bottle-fed with colostrum

individually to make sure they were nursed to appetite.

Mixed colostrum was collected from their dams

within 1 h after birth, which was designated as 0 h,

subsequent milkings and feedings were performed at

6 h intervals for the ®rst day and at 12 h intervals

thereafter. Blood samples from the jugular vein of kids

for glucose, g-globulin and cortisol determinations

were collected exactly at 0, 6, 12, 18, 24, 36 h, and

2, 3, 4, 5 days of age. After centrifugation the serum

was removed and stored at ÿ208C until analyzed.

2.2. ACTH administration

Kids at age of 5 days were administrated i.v. with 1

IU ACTH (ACTH1±39, Sigma, A-6303, from porcine

pituitary, 89 IU/mg) 1.5 h following the ®fth day

sampling. ACTH was diluted in normal saline to a

total volume of 1 ml before use. A jugular blood

sample was obtained at 0.5 h following administration

of ACTH. The dosage of ACTH and the regimes of

injection and sampling mainly followed the reports of

Evans et al. (1988), Parraguez et al. (1989) and

Verkerk et al. (1994). In their studies, 10 IU of ACTH

for a mean weight of 471 kg cows was enough to reach

the peak cortisol response equivalent to that of 32-fold

doses at 30 min following ACTH administration (Ver-

kerk et al., 1994). Parraguez et al. (1989) reported that

the 24 h diurnal secretion pattern of plasma cortisol

256 J.C. Chen et al. / Small Ruminant Research 33 (1999) 255±262

was not yet established in newborn sheep younger than

15 days of age, while Evans et al. (1988) showed that

the effect of jugular venipuncture sampling on plasma

cortisol concentration was recovered by 30 min.

Therefore, although kids were administrated with

ACTH at different hours of the day depending on

their delivery time, and blood samples were not

collected via a catheter as has been commonly done

for samples destined for cortisol analysis, the protocol

used in the present experiment should not affect the

interpretation of the results.

2.3. Laboratory analyses

Samples of blood serum were assayed for g-globulin

as described previously (Chen et al., 1999) by elec-

trophoresis with Helena Titan agarose gel plate (Titan

Gel Serum Protein System, Cat. No. 33041, Helena

Laboratories, Beaumont, TX). Serum glucose concen-

trations were measured enzymatically (SIGMA

DIAGNOSTICS1, Glucose HK kit, Cat. No. 16-20,

Sigma) by hexokinase and glucose-6-phosphate dehy-

drogenase. Serial dilutions of glucose standard

(100 mg/dl, Cat No.16-100, Sigma) were used to

determine the glucose concentration in samples where

duplicate or triplicate measurement in one assay was

conducted.

Cortisol concentrations in serum were determined

by a competitive chemiluminescent immunoassay.

This assay was conducted using the Ciba Corning

ACS:180TM Automated Chemiluminescence Systems.

Reagents, which include acridinium ester labeled

cortisol and rabbit anti-cortisol antibody bound to

monoclonal mouse anti-rabbit IgG antibody coupled

to paramagnetic particles, were supplied by Ciba

Corning Diagnostics (Med®eld, MA). The ACS:180

system was calibrated and run with a quality control

program before assaying the samples, and all the

assays were ®nished within 4 h. According to the

kit information, the ACS cortisol assay is highly

speci®c with <7.5% cross-reactivity with any poten-

tially competing endogenous steroids. The sensitivity

of the assay, as measured by subtracting two SD from

the mean of ACS cortisol zero standard, was up to

75 mg/dl with a minimum detectable concentration of

0.20 mg/dl. The accuracy of this assay for 513 serum

samples in the range of 0.19±56.98 mg/dl was highly

correlated (r � 0.97) with an alternate ¯uorescence

polarization immunoassay method. The intra- and

inter-assay CV for six samples ranging between

3.04±36.67 mg/dl for triplicate analyses in six assays

on four systems was 5.7±7.6% and 9.1±9.7%, respec-

tively.

2.4. Statistical analysis

Of the total 43 kids born to 17 does, those with

serum cortisol concentrations at birth greater than the

overall mean plus 0.5 SD were designated as a `high'

cortisol group and those less than the overall mean

minus 0.5 SD were designated as `low' cortisol group.

Kids with serum cortisol concentration ranged

between mean � 0.5 SD were omitted from this

experiment. The mean values for birth weight,

ADG, concentrations of serum cortisol, glucose,

and g-globulin at birth, averages over the ®rst 5 days

(0±5 days) and after ACTH administration were com-

pared between `high' and `low' groups by means of

the student's t-test (SAS, 1993). The pro®les of serum

cortisol, glucose, and g-globulin concentrations for

each group are reported as mean � SE. The mean

values were also compared between groups at each

corresponding age.

3. Results and discussion

3.1. Serum cortisol concentrations of neonatal kids

and their responsiveness to ACTH

The overall mean (� SE) serum cortisol concentra-

tion at birth was 7.68 � 0.39 mg/dl for the total 43

kids. After grouping, concentrations of serum cortisol

for `high' (n � 14) and `low' (n � 15) cortisol groups

of kids were 10.59 � 0.43 and 5.09 � 0.28 mg/dl at

birth, and were 2.87 � 0.15 and 1.96 � 0.10 mg/dl for

the averages over the ®rst 5 days of life, respectively

(Table 1). The pro®les of serum cortisol concentration

over the ®rst 5 days of life for these two groups of

normal, non-fasted kids show a drastic drop during the

®rst 6 h especially for the `high' group (Fig. 1), they

then leveled off gradually. No differences (p > 0.05) in

serum cortisol concentration between groups were

found after birth except at 36 h (Fig. 1). As for ACTH

responsiveness, the serum cortisol level measured at

1.5 h before and 0.5 h following ACTH administration

J.C. Chen et al. / Small Ruminant Research 33 (1999) 255±262 257

were also not different (p > 0.05) between groups

(Fig. 2).

Signi®cant increase in fetal cortisol concentration

since late gestation has been widely reported in many

species (Currie and Thorburn, 1977; Nightengale and

Stott, 1981; McMillen et al., 1987; Spencer et al.,

1989; Agarwal et al., 1992; Nagaya and Widmaier,

1993). It is expected during this period as the fetus

prepares for the trauma of birth and adaptation to its

postnatal environment (Nathanielsz, 1976). Maternal

plasma cortisol concentrations also rise slightly before

delivery but increase signi®cant only during delivery

(Hudson et al., 1976; Randall, 1983). Plasma cortisol

concentration was found to be considerably higher in

the newborn calf than in the dam at parturition (Hud-

son et al., 1976). It was also indicated that the fetal

adrenal gland responds to stimuli independent of

maternal response or else it responds to a much greater

Table 1

Means (� SE) of birth weight, ADG, serum concentrations of

cortisol and glucose at birth and averaged over the first 5 days of

life in Nubian kids

Variables Birth serum cortisol levelb

High (n � 14) Low (n � 15

Birth weight (kg) 2.93 � 0.13 3.01 � 0.12

ADG (kg/d) 0.16 � 0.02 0.12 � 0.01a

Serum cortisol (mg/dl)

At birth 10.59 � 0.43 5.09 � 0.28a

Days 0±5 2.87 � 0.15 1.96 � 0.10a

Serum glucose (mg/dl)

At birth 106.8 � 7.5 90.9 � 5.6

Days 0±5 116.7 � 3.4 101.4 � 2.5a

a Significantly different (p < 0.05) between groups of kids.b Kids designated as `high' and `low' birth serum cortisol levels

had cortisol concentrations � 0.5 SD different than the overall

mean 7.48 (� 0.39) obtained from a total of 43 kids.

Fig. 1. Mean serum cortisol concentrations of groups of goat kids born with high (&, n � 14) or low (*, n � 15) serum cortisol levels during

the first 5 days of age. Vertical lines denote SE. *p < 0.01, significantly different between groups at the specified age.

Fig. 2. Mean serum cortisol concentrations of groups of goat kids

born with high or low serum cortisol levels at 1.5 h before and 0.5 h

after i.v. ACTH1±39 administration (1.0 IU) at 5 days of age.

258 J.C. Chen et al. / Small Ruminant Research 33 (1999) 255±262

degree (Stott and Reinhard, 1978). Therefore, the

maternal effect on kids' serum cortisol level at birth

should be minimum. In the present study, the con-

siderably higher serum cortisol concentrations at birth

in kids of `high' cortisol group compared to those of

`low' cortisol group suggest, to a certain degree, their

higher prenatal HPA axis activity. Although the `high'

cortisol group still had greater average serum cortisol

level than the `low' cortisol group during the ®rst 5

days of life (2.87 � 0.15 vs. 1.96 � 0.10 mg/dl,

p < 0.05, Table 1), this high HPA activity was appar-

ently lost gradually following birth, so that by 5 days

of age, there were was a similar adrenocortical func-

tion between two the groups as was re¯ected by the

similar ACTH responsiveness (Fig. 2). None of the

possible mechanisms that might result in high pre-

natal HPA axis activity was intended to be investigated

in the present experiment, but it was apparently not

closely related to the neonatal adrenocortical function.

3.2. Serum glucose concentrations of neonatal kids

Fig. 3 shows changes in serum levels of glucose in

newborn kids during the ®rst 5 days of life. No

differences (p > 0.05) in concentrations were found

between kids of `high' and `low' cortisol groups at

birth. Although the levels were also not different

between groups for most of the time points measured

except at 2 and 5 days; overall, kids with `high' birth

cortisol levels had about 15% greater (p < 0.05) aver-

age serum glucose concentration during the ®rst 5

days (Table 1, 116.7 � 3.4 vs. 101.4 � 2.5 mg/dl,

respectively). Both groups of kids were apparently

normoglycemic during the experimental period even

before nursing.

The incidence of neonatal hypoglycemia (plasma

glucose <60 mg/dl) in rats was reported to be >20%,

with most cases occurring during 0±4 h and 18±22 h

following birth (Nagaya and Widmaier, 1993). It was

also found in the same report that low glucose levels in

the ®rst hours after birth were signi®cantly associated

with high plasma glucocorticoid and ACTH levels;

therefore, they suggested that the HPA axis appears to

be active from birth and might be responsive to

hypoglycemia stress during this early period (Nagaya

and Widmaier, 1993). In the present study, despite the

signi®cant difference in serum cortisol concentration

at birth between `high' and `low' cortisol kids, serum

glucose at birth for both groups were similar and at

normal levels. It is postulated that mechanisms of fetal

glucose stasis might have been active prenatally,

probably through balanced hepatic glycogenolysis

and gluconeogenesis, but there was a lack of linkage

between levels of serum cortisol and glucose during

early neonatal period of kids; similar results have been

found in rat pups older than 10 days by Widmaier

(1990). Differences in results obtained from different

species might be related to the state of maturity of

the young animals born. Stable levels of serum

glucose throughout the very early neonatal days

suggest appropriate intestinal absorption and liver

functions of kids.

Fig. 3. Mean serum glucose concentrations of groups of goat kids born with high (&, n � 14) or low (*, n � 15) serum cortisol levels during

the first 5 days of age. Vertical lines denote SE. *p < 0.05, **p < 0.01, significantly different between groups at the specified age.

J.C. Chen et al. / Small Ruminant Research 33 (1999) 255±262 259

3.3. Birth weight and body weight gains of kids

The mean birth weight and ADG over the ®rst 5

days of neonatal life for the `high' and `low' cortisol

kids are listed in Table 1. There were no differences

(p > 0.05) in birth weight between these two groups

regardless of the signi®cant difference in serum cor-

tisol concentration at birth. However, kids born with

higher serum cortisol concentrations gained about

33% more weight than those with lower concentration

(0.16 � 0.02 vs. 0.12 � 0.01 kg/day; p < 0.05). The

accumulated body weight gains shown in Fig. 4 dis-

play the consistent better growth performance of kids

from the `high' cortisol group.

It is well established that glucocorticoid hormones

have catabolic effects in the muscle and can retard

growth rate in young animals when they are present in

high concentrations or can stimulate growth rate in

normal female rats through the suppression by anti-

ACTH antibodies (Sillence et al., 1992). The study of

Klemcke et al. (1993) indicated 70±199% greater in

plasma cortisol concentrations during Days 3±7 of

neonatal life and enhanced sensitivity of adrenocor-

tical cell response to ACTH at 7 days of age in low

birth weight pigs. They postulated that increased

adrenal function is initiated pre-natally and causes

some instances of low birth weight; however, they did

not measure the plasma cortisol levels of the piglets

prior to 3 days of age. Since the fetal cortisol level at

birth is not likely to be affected by maternal cortisol, it

should be related to the pre-natal HPA axis activity.

Results from our study suggest that high pre-natal

adrenal activity does not necessarily result in low birth

weights, and kids with more active pre-natal HPA axis

do not necessarily have a more active adrenocortical

function post-natally. Age-related decreases in plasma

cortisol and sensitivity of adrenocortical cell response

to ACTH were also observed by Kattesh et al. (1990)

and Klemcke et al. (1993) during 3±7 days of age in

neonatal pigs. The present study found no difference

in ACTH responsiveness at 5 days of age (Fig. 2)

between the two groups of kids. It is suggested that

dramatic changes in adrenocortical function occur

during perinatal development. Fetal and neonatal

growth are presumably related with the adrenocortical

function in a different manner.

3.4. Serum g-globulin concentrations of neonatal

kids

The serum g-globulin pro®les of `high' and `low'

cortisol groups of kids during the ®rst 5 post-partum

days are shown in Fig. 5. Kids born with high

serum cortisol concentrations had similar (p > 0.05)

mean serum g-globulin concentrations than the `low'

cortisol group prior to 12 h of age, but reached a

greater (p < 0.05) mean peak level around 18 h

of age and had a consistently greater concentration

Fig. 4. Accumulated weight gains of groups of goat kids born with high (&, n � 14) or low (*, n � 15) serum cortisol levels during the first

5 days of age. Vertical lines denote SE. *p < 0.05, significantly different between groups at the specified age.

260 J.C. Chen et al. / Small Ruminant Research 33 (1999) 255±262

thereafter since then during the 5 days experimental

period.

The discovery by Halliday (1959) that glucocorti-

coids induce precocious closure of the intestine of

nursing rats was not always detected in large animals

(Stott, 1980; Stott and Reinhard, 1978; Nightengale

and Stott, 1981). The recent study of Hough et al.

(1990) obtained different results that demonstrated

low cortisol treatment, and not high cortisol treatment,

initiated precocious closure to Ig absorption in lambs.

They also found that immaturity might delay gut

closure and the time of gut closure for different Ig

classes was different, possibly re¯ecting selectivity of

transport system and molecular weight difference of

the various Igs. It has long been suggested by Patt

(1977) that absorption of antibodies is not maximal

unless cortisol in plasma is adequate, and that the high

perinatal cortisol in farm animals has a net bene®t on

post-natal absorption of antibodies regardless of any

possible effect they might have on closure. In the

present study, elevated serum g-globulin levels of kids

with higher serum cortisol concentration at birth was

observed to be related with greater body weight gains

during the neonatal period. It is implied that the

bene®cial effect of active adrenocortical function on

neonatal immunity and growth performance might

have started prenatally through mechanisms not only

modifying the development of important organs such

as intestine and live,r but also, possibly, the post-natal

ingestive activities and suckling ability.

Acknowledgements

Financial support was received from the National

Science Council (NSC85-2321-B-005-078). We thank

Mr. S.S. Wuen of the Taiwan Livestock Research

Institute for providing the animals and facilities and

the cooperation granted in his Institute. Appreciation

is also extended to Mr. D.Y.C. Yang and Mr. W.J.S. Su

for the preparation of this manuscript.

References

Agarwal, S.P., Rai, A.K., Khanna, N.D., 1992. Hormonal studies in

post-partum female camels and their neonates. Theriogenology

38, 735±747.

Bassett, J.M., Thorburn, G.P., 1969. Fetal plasma corticosteroids

and the initiation of parturition in sheep. J. Endocrinol. 44,

285±286.

Bate, L.A., Hacker, R.R., 1985. The influence of the sow's adrenal

activity on the ability of the piglet to absorb IgG from

colostrum. Can. J. Anim. Sci. 65, 77±85.

Bate, L.A., 1991. Modifications in the aggressive and ingestive

behavior of the neonatal piglet as a result of prenatal elevation

of cortisol in the dam. Appl. Anim. Behav. Sci. 30, 299±306.

Chen, J.C., Chang, C.J., Peh, H.C., Chen, S.Y., 1999. Serum protein

levels and neonatal growth rate of Nubian goat kids in Taiwan.

Small Rumin. Res., in press.

Clark, S.L., 1971. The effect of cortisol and BUDR on cellular

differentiation in the small intestine in suckling rats. Am. J.

Anat. 132, 319±338.

Currie, W.B., Thorburn, G.D., 1977. Parturition in goats: Studies on

the interactions between the fetus, placenta, prostaglandin F

Fig. 5. Mean serum g-globulin concentrations of groups of goat kids born with high (&, n � 14) or low (*, n � 15) serum cortisol levels

during the first 5 days of age. Vertical lines denote SE. **p < 0.01, *p < 0.05, significantly different between groups at the specified age.

J.C. Chen et al. / Small Ruminant Research 33 (1999) 255±262 261

and progesterone before parturition at term, or at parturition

prematurely induced by corticotrophin infusion of the fetus. J.

Endocrinol. 73, 263±278.

Evans, F.D., Christopherson, R.J., Aherne, F.X., 1988. Develop-

ment of the circadian rhythm of cortisol in the gilt from

weaning until puberty. Can. J. Anim. Sci. 68, 1105±1111.

Halliday, R., 1959. The effect of steroid hormones on the

absorption of antibody of the young rats. J. Endocrinol. 18,

56±66.

Hargrave, B.Y., Rose, J.C., 1986. By 95 days of gestation CRF

increases plasma ACTH and cortisol in ovine fetuses. Am. J.

Physiol. 250, E422±E427.

Hough, R.L., McCarthy, F.D., Thatcher, C.D., Kent, H.D., Ever-

sole, D.E., 1990. Influence of glucocorticoid on macromole-

cular absorption and passive immunity in neonatal lambs. J.

Anim. Sci. 68, 2459±2464.

Hudson, S., Mullford, M., Whittlestone, W.G., Payne, E., 1976.

Bovine plasma corticoids during parturition. J. Dairy Sci. 19,

744±746.

Kattesh, H.G., Charles, S.F., Baumbach, G.A., Gillespie, B.E.,

1990. Plasma cortisol distribution in the pig from birth to six

weeks of age. Biol. Neonate 58, 220±226.

Klemcke, H.G., Lunstra, D.D., Brown-Borg, H.M., Borg, K.E.,

Christenson, R.K., 1993. Association between low birth weight

and increased adrenocortical function in neonatal pigs. J. Anim.

Sci. 71, 1010±1018.

Magyar, D.M., Fridshal, D., Elsner, C.W., Glatz, T., Eliot, J., Klein,

A.M., Lowe, K.C., Buster, J.E., Nathanielsz, P.W., 1980. Time-

trend analysis of plasma cortisol concentrations in the fetal

sheep in relation to parturition. Endocrinology 107, 155±159.

McMillen, I.C., Thorburn, G.D., Walker, D.W., 1987. Diurnal

variations in plasma concentrations of cortisol, prolactin,

growth hormone and glucose in the fetal sheep and pregnant

ewe during late gestation. J. Endocrinol. 114, 65±72.

McMillen, I.C., Jenkin, G., Haji-Baba, A.S., Browne, C.A.,

Thorburn, G.D., 1989. Effect of g3 or g2 melanocyte stimulating

hormone on steroidogenesis in the fetal sheep during late

gestation. Life Sci. 44, 563±569.

Nagaya, M., Widmaier, E.P., 1993. Twenty-four hour profiles of

glucose, corticosterone and adrenocorticotropic hormone dur-

ing the first postnatal day in rats. Biol. Neonate 64, 261±268.

Nathanielsz, P.W., 1976. Fetal endocrinology: An experimental

approach. In: Animal Models in Fetal Medicine. Monographs

in Fetal Physiology, vol. 1, Elsevier, North-Holland, NY.

Nightengale, G.T., Stott, G.H., 1981. Adrenal response of the

newborn calf to acute inanition and colostral feeding. J. Dairy

Sci. 64, 236±240.

NRC, 1981. Nutrient requirements of goats. Natl. Acad. Sci., Natl.

Res. Council, Washington, DC, 91 pp.

Parraguez, V.H., Vergara, M., Riquelme, R., Raimann, R., Llanos,

A.J., Seron-ferre, M., 1989. Ontogeny of the circadian rhythm

of cortisol in sheep. Biol. Reprod. 40, 1137±1143.

Patt, J.A., 1977. Factors affecting the duration of intestinal

permeability to macromolecules in newborn animals. Biol.

Rev. 52, 411±429.

Patt, J.A., Eberhart, R.J., 1974. Effect of elevated corticosterone

levels on serum gamma globulin concentrations in newborn

rats. Proc. Soc. Exp. Biol. Med. 145, 200±202.

Randall, G.C.B., 1983. Changes in the concentrations of corticos-

teroids in the blood of fetal pigs and their dams during late

gestation and labor. Biol. Reprod. 29, 1077±1084.

Rose, J.C., Meis, P.J., Urban, R.B., Greiss Jr., F.C., 1982. In vivo

evidence for increased adrenal sensitivity to adrenocorticotro-

pin-(1±24) in the lamb fetus late in gestation. Endocrinology

111, 80±85.

SAS, 1993. SAS/STAT1 User's Guide. Version 6, 4th edn., vol. 2,

Statistical Analysis Systems Institute, Inc., Cary, NC.

Sillence, M.N., Rodway, R.G., 1987. Effects of metyrapon and

etomidate on adrenal function and growth rate in female rats. J.

Endocrinol. 113, 473±478.

Sillence, M.N., Jones, M.R., Lowry, P., Bassett, J.R., 1992. Passive

immunization with antiserum to adrenocorticotropin increases

weight gain in normal female rats. J. Anim. Sci. 70, 1382±1388.

Spencer, G.S.G., Hallett, K.G., Beermann, U., MacDonald, A.A.,

1989. Changes in the levels of growth hormone, insulin,

cortisol, thyroxine and somatomedin-C/IGF-I, with increasing

gestational age in the fetal pig, and the effect of thyroidectomy

in utero. Comp. Biochem. Physiol. 93, 467±472.

Stott, G.H., 1980. Immunoglobulin absorption in calf neonates with

special considerations of stress. J. Dairy Sci. 63, 681±688.

Stott, G.H., Reinhard, E.J., 1978. Adrenal function and passive

immunity in the dystocial calf. J. Dairy Sci. 61, 1457±1461.

Verkerk, G.A., Macmillan, K.L., Mcleay, L.M., 1994. Adrenal

cortex response to adrenocorticotropic hormone in dairy cattle.

Domestic Anim. Endocrinol. 11, 115±123.

Widmaier, E.P., 1990. Glucose homeostasis and hypothalamic±

pituitary±adrenocortical axis during development in rats. Am. J.

Physiol. 259, E601±E613.

Wood, C.E., 1991. Cortisol inhibits ACTH secretion in late-

gestation fetal sheep. Am. J. Physiol. 260, R385±R388.

262 J.C. Chen et al. / Small Ruminant Research 33 (1999) 255±262