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Journal of Clinical Endocrinology and Metabolism
Copyright © 1997 by The Endocrine Society
Vol. 82, No. 7
Printed in U.S.A.
Changes in Serum Immunoreactive and Bioactive
Growth Hormone Concentrations in Boys with
Advancing Puberty and in Response to a 20-Hour
Estradiol Infusion*
AYSE PINAR CEMEROGLU†, ARIEL L. BARKAN, GAD B. KLETTER‡,
INESE Z. BEITINS§, AND CAROL M. FOSTER
Department of Pediatrics, Division of Endocrinology, and the Department of Internal Medicine (A.B.),
University of Michigan Medical School, Ann Arbor, Michigan 48109
ABSTRACT
Acceleration of linear growth during puberty is associated with
increased GH secretion, although the relationship between growth
and GH is complex. As GH exists as a family of isoforms, some of which
may not be identified by immunoassay, there may be alterations in
isoform secretion during pubertal maturation that result in increased
growth. The changes in serum immunoreactive and bioactive GH
concentrations across pubertal maturation were determined in 30
boys, aged 6.5–19.3 yr, with idiopathic short stature or constitutional
delay of adolescence. Data were grouped as follows: 1) 6 prepubertal
boys with bone age 7 yr or less; 2) 5 prepubertal boys with bone age
of more than 7 yr; 3) 10 boys in early puberty; 4) 9 boys with mid- to
late puberty. Blood was obtained every 20 min from 2000 – 0800 h. An
equal aliquot of each serum sample was pooled for determination of
GH by bio- and immunoassays. The mean serum immunoreactive GH
concentration increased from 2.1 6 0.3, 1.8 6 0.3, and 2.9 6 0.5 mg/L
in groups 1, 2, and 3, respectively, to a peak of 4.6 6 0.7 mg/L in group
4 (P , 0.05 vs. groups 1–3). The mean serum GH bioactivity was 48 6
13 mg/L in group 1 and declined to 39 6 8 and 31 6 3 mg/L in groups
2 and 3, increasing to a maximum of 64 6 15 mg/L in group 4 (P , 0.05
vs. group 3). The ratio of bioactive to immunoreactive GH suggests
that the biopotencies of secreted isoforms do not increase during
pubertal maturation. The role of E2 in increasing GH secretion was
characterized in 8 additional early pubertal boys. Each boy received
a saline infusion from 1000 – 0800 h, followed 1 week later by an
infusion of E2 at 4.6 nmol/m2zh. Blood was obtained every 15 min from
2200 – 0800 h for GH and LH and every 60 min for E2 and testosterone.
An equal aliquot of each overnight serum sample was pooled for
insulin-like growth factor I (IGF-I) and GH by immuno- and bioassays. The mean serum LH concentration decreased from 5.0 6 0.9 to
2.3 6 0.6 IU/L (P , 0.01), and the E2 concentration increased from
22 6 4 to 81 6 26 pmol/L (P , 0.01) during saline and E2 infusions,
respectively. Mean serum GH concentrations as measured by immunoassay were similar during both infusions (6.6 6 1.4 vs. 9.7 6 2.1
mg/L; saline vs. E2 infusion, respectively). In contrast, the mean serum
GH concentration, as measured by bioassay, decreased from 48 6 10
mg/L during saline infusion to 16 6 3 mg/L during E2 infusion (P ,
0.05). The mean serum IGF-I concentration also decreased significantly from 116 6 17 to 93 6 15 mg/L (saline vs. E2 infusion, respectively; P , 0.05). Thus, although mean overnight serum GH concentrations increase in late puberty, whether measured by immuno- or
bioassay, an acute increase in E2 produces an acute decline in serum
GH bioactivity and a lesser decline in the serum IGF-I concentration.
These unexpected changes indicate that E2 may affect pubertal
growth and GH secretion in a complex or biphasic manner depending
on the context in which it is administered. (J Clin Endocrinol Metab
82: 2166 –2171, 1997)
P
suggests that factors other than the GH concentration may
influence the rate of growth during pubertal maturation.
Alternatively, as GH is produced and secreted as a family of
isoforms (10 –12), and these isoforms may not be equally
recognized by standard immunoassays, pubertal growth acceleration may be influenced by a change in the relative
biopotency of secreted and circulating GH.
It has been difficult to assess GH bioactivity in serum
because the available assays have either been relatively insensitive or have had nonphysiologic end points, limiting
their utility (13–17). Recently, we developed an in vitro bioassay (18) that has enabled us to examine the changes in
nocturnal serum bioactive as well as immunoreactive GH
concentrations in a cross-sectional study of 30 boys in different stages of puberty. We hypothesized that the biopotencies of circulating GH isoforms increase more than the
immunoreactive GH concentration during puberty, which
may explain the nonlinear relationship between the serum
immunoreactive GH concentration and pubertal growth.
Studies in patients with constitutional delay of growth and
UBERTAL growth in boys is associated with a marked
acceleration of linear growth velocity, which peaks
during late puberty. Although the rate of growth during
puberty is associated with an increase in the serum GH
concentration (1–7), the relationship is not linear (8, 9). This
Received January 30, 1997. Revision received March 21, 1997.
Accepted March 31, 1997.
Address all correspondence and requests for reprints to: Dr. Ayse
Pinar Cemeroglu, D3252 Medical Professional Building, Box 0718, 1500
East Medical Center Drive, Ann Arbor, Michigan 48109-0718.
* This work was supported by NIH Grants DK-43513 and HD-16000
and the Kughn Clinical Research Center (M01-RR00042). Presented in
part at the 76th Annual Meeting of The Endocrine Society, Anaheim, CA,
1994, and at 65th Annual Meeting of the Society for Pediatric Research,
Washington, D.C., 1996.
† Recipient of a fellowship award from the Genentech Foundation for
Growth and Development and supported in part by Eli Lilly Co. Funding for Fellowship Education and Research.
‡ Current address: Department of Pediatrics, University of Washington, Seattle, Washington 98105.
§ Current address: National Center for Research Resources, National
Institutes of Health, Bethesda, Maryland 20892.
2166
PUBERTY, E2, AND GH IN BOYS
hypogonadism suggest that testosterone (T) replacement
augments GH secretion and promotes the growth rate (19,
20). However, in pubertal boys, the estrogen concentration
increases as well, mainly through peripheral aromatization
of T (21). Thus, the relative importance of increased estrogen
vs. T concentration on the pubertal increase in growth rate
and GH secretion in boys is still not well understood (1).
Estrogen receptor blockade with tamoxifen has been shown
to diminish GH secretion in boys, providing indirect evidence for the role of estrogens in the male pubertal growth
spurt (22). We have previously demonstrated that acute T
infusion does not alter nocturnal GH secretion in pubertal
boys, suggesting that T must be aromatized to estradiol (E2)
to become effective (23). Thus, we designed another study to
examined the effect of a 20-h E2 infusion on nocturnal serum
immunoreactive and bioactive GH concentrations in early
pubertal boys, testing the hypothesis that the pubertal increase in the serum GH concentration in boys may be related
to an increased estrogen concentration.
2167
samples obtained between 2000 – 0800 h for determination of serum
immunoreactive and bioactive GH, LH, FSH, E2, T, insulin-like growth
factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3).
E2 infusion study
Each boy was studied twice, 1 week apart. Boys spent the first day
of each study acclimatizing to the unit. On the following day, an iv access
was established in one forearm for administration of saline or E2, and
a second heparinized iv cannula was placed in the opposite forearm to
obtain blood samples. During the first study, saline was infused at 10
cc/h beginning at 2200 h and continuing through 0800 h. Blood was
obtained at 15-min intervals from 1200 – 0800 h for serum GH determinations. E2 and T concentrations were determined every 60 min. The
boys were readmitted 1 week later for an identical protocol, except that
saline was replaced with an infusion of E2. The E2 (Sigma Chemical Co.,
St. Louis, MO) was dissolved in ethanol, diluted into saline to a final
concentration of 4.6 nmol/m2 body surface areaz10 cc saline and infused
at a rate of 10 cc/h to approximate the adult blood production rate (26).
For blood samples obtained during saline or E2 infusion, an equal aliquot
of each serum sample from 2200 – 0800 h was also pooled for determination of immunoreactive and bioactive T, E2, LH, and IGF-I concentrations.
Subjects and Methods
Hormone assays
Subjects
For all patients in the E2 infusion study, except patient 7, the serum
immunoreactive GH concentration was determined using a double antibody RIA (27). Standards and antibodies were obtained from the National Hormone and Pituitary Program (Baltimore, MD) and the NIDDK.
The sensitivity of the assay was 0.5 mg/L, and the intra- and interassay
coefficients of variation (CVs) were less than 4% and 10%, respectively.
For patient 7 in the E2 infusion study, the serum immunoreactive GH
concentration was determined by IFMA using a Delfia kit purchased
from Wallac (Gaithersburg, MD). The immunoreactive GH concentrations in the samples assayed every 15 min overnight were used only to
study the GH pulse characteristics and were not used to make comparisons with GH concentrations detected by bioassay. A comparison of
the RIA and the IFMA was presented previously (28), and the assays
were found to be comparable in terms of peaks detected and GH profile
characteristics. For immuno- and bioassay comparisons, an equal aliquot
of each sample was pooled for a single determination of serum GH
concentration by IFMA and bioassay for all patients in the cross-sectional or E2 infusion studies.
Serum GH bioactivity was determined based on the ability of GH to
suppress glucose metabolism in 3T3-F442A adipocytes as described
previously (18). The standard was 22,000-dalton recombinant DNAderived human GH and was a gift from Lilly Research Laboratories
(Indianapolis, IN). The assay sensitivity was 3 mg/L, and the intra- and
interassay CVs were 9% and 17%, respectively.
Serum E2 and T concentrations were determined by RIA using a kit
obtained from Diagnostic Products Corp. (Los Angeles, CA). The assay
sensitivity for E2 was 18 pmol/L, and the intra- and interassay CVs were
8% and 15%, respectively. The assay sensitivity for T was 0.35 nmol/L,
and intra- and interassay CVs were 8% and 15%, respectively.
The clinical characteristics of the 30 boys in the cross-sectional study
and those of the 8 boys in the E2 infusion study are shown in Tables 1
and 2 respectively. All of the boys studied had either idiopathic short
stature or delayed adolescence, but were otherwise healthy and were not
taking any medications. Thyroid function tests were normal. For the
purpose of comparison, the boys in the cross-sectional study are divided
into 4 groups as follows: group 1, 6 boys with stage I puberty with a bone
age of 7 yr or less (young prepubertal); group 2, 5 boys in stage I puberty
with a bone age of more than 7 yr (prepubertal); group 3, 10 boys in stage
II puberty (early pubertal); and group 4, 9 boys in stage III and IV
puberty (mid- to late pubertal). Subjects who had subnormal responses
to GH provocative tests (insulin and arginine tolerance tests) were excluded from the study.
Protocols
The protocols were approved by the institutional review board of the
University of Michigan. Informed consent was obtained from a parent
and assent from the child before the study. All studies were carried out
in the Kughn Clinical Research Center of the University of Michigan. All
samples were immediately frozen after they were obtained and were
thawed just before assay.
Cross-sectional study
An iv heparinized cannula was placed in a forearm vein 2 h before
the study. Blood was obtained every 20 min from 2000 – 0800 h next
morning. An equal aliquot of each serum sample was pooled from
TABLE 1. Clinical characteristics of 30 boys in a cross-sectional study
Groups
Pubertal
stagea
Young prepubertal
I
6
Prepubertal
I
5
Early pubertal
II
10
III/IV
9
Midlate pubertal
n
Values are the mean 6 SE.
a
Determined by the method of Tanner (24).
b
Ranges for chronological age and bone age are given in parentheses.
c
Determined by the method of Greulich and Pyle (25).
Age (yr)b
Bone age (yr)b,c
7.6 6 0.4
(6.5–9.4)
12.3 6 0.6
(10.1–13.5)
14.3 6 0.4
(12.1–15.8)
15.6 6 0.6
(14.5–19.3)
5.4 6 0.5
(4.5–7.0)
10.8 6 0.3
(9.6 –11.5)
12.4 6 0.5
(9.5–14.0)
13.2 6 0.5
(12.5–16.0)
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CEMEROGLU ET AL.
TABLE 2. Clinical characteristics of boys in the E2 infusion study
Subject no.
Pubertal
stagea
Age
(yr)
Bone age
(yr)b
Ht
(cm)
Wt
(kg)
1
2
3
4
5
6
7
8
II
II
I–II
III
II
II
II
III
13.8
15.2
13.8
13.9
15.2
15.9
14.3
15.7
10.0
11.0
11.5
11.5
12.0
12.0
12.5
NDc
143.4
141.7
140.9
144.6
146.5
149.5
147.6
182.5
34.1
31.8
33.0
37.4
33.3
40.2
31.4
136.6
a
Determined by the method of Tanner (24).
Determined by the method of Greulich and Pyle (25).
c
Not done.
b
TABLE 3. Laboratory characteristics of the 30 boys in the cross-sectional study
LH (IU/L)
FSH (IU/L)
T (nmol/L)
E2 (pmol/L)
Group 1
Group 2
Group 3
Group 4
0.1 6 0a
0.4 6 0.2b
0.4 6 0.03b
20.2 6 1.9
0.7 6 0.3b
1.5 6 0.5
0.4 6 0.06
18.4 6 0
3.1 6 0.6
1.6 6 0.3
4.6 6 1.3
23.9 6 5.6
5.0 6 1.1
3.3 6 1.5
10.8 6 2.7
43.5 6 9.5a
Data are given as the mean 6 SE.
a
P , 0.05 vs. all other groups.
b
P , 0.05 vs. groups 3 and 4.
In the E2 infusion study, serum IGF-I concentrations were determined
using a double antibody RIA after first extracting the serum samples
with acetic acid and ethanol as described previously (29). The polyclonal
antibody to IGF-I was obtained from the National Hormone and Pituitary Program, and the standard was purchased from Mallinkrodt Specialty Chemicals (St. Louis, MO). The intraassay CV was 8.8%, and all
samples were measured in a single assay. The assay sensitivity was 1.0
ng/mL. Serum IGF-I and IGFBP-3 measurements in the cross-sectional
study were performed using kits obtained from Endocrine Sciences
(Calabasas Hills, CA). The assay sensitivity for IGF-I was 15 ng/mL, and
the intra- and interassay CVs were 9% and 13%, respectively. The assay
sensitivity for IGFBP-3 was 0.37 mg/L, and intra- and interassay CVs
were 9% and 12%, respectively.
Serum LH and FSH concentrations were determined by IFMA using
Delfia kits. The assay sensitivity for LH was 0.05 IU/L, and the intra- and
interassay CVs were 5% and 6%, respectively. The assay sensitivity for
FSH was 0.05 IU/L, and the intra- and interassay CVs were 3.0% and
4.5%, respectively.
Statistical analyses
All data were transformed logarithmically before analysis. Comparisons between each group in the cross-sectional study were made using
factorial ANOVA. The data are represented as the mean 6 se. For the
E2 infusion study, comparisons between treatments were made by Student’s paired t test for single comparisons or repeated measures
ANOVA for multiple comparisons.
Pulse detection. Pulses of GH were determined using the DETECT
method of Oerter et al. (30). The false positive peak detection level was
set at less than 1% using the predicted variance model. All values less
than assay sensitivity were assigned a value of assay sensitivity. Missing
values were not replaced. Peak amplitudes were derived by calculating
the difference between the peak and the prepeak nadir. All accepted
peaks had an amplitude at least twice the assay sensitivity.
Results
Cross-sectional study
Mean overnight serum LH, FSH, E2, and T concentrations. In
addition to physical signs, biochemical markers of pubertal
maturation in the subjects were assessed by determining
serum LH, FSH, T, and E2 concentrations in the overnight
pools. Serum LH, FSH, E2, and T concentrations were the
lowest in young prepubertal and prepubertal groups and
increased as pubertal maturation advanced, peaking in the
mid- to late pubertal group (Table 3).
Mean overnight serum IGF-I and IGFBP-3 concentrations (Fig. 1).
The mean overnight serum IGF-I concentration increased
from 106 6 27 mg/L in group 1 to 169.9 6 15 mg/L in group
2 to 195.7 6 34.7 mg/L in group 3, and to a peak concentration
of 325.4 6 54.7 mg/L in group 4 boys (P ,0.05 vs. group 1).
Boys in the mid- to late puberty (group 4) also had the
greatest concentration of mean overnight serum IGFBP-3
(P , 0.05 vs. group 1).
Mean overnight serum GH concentrations determined by immunoassay and bioassay. The mean overnight serum GH concentration determined by immunoassay was 2.1 6 0.3 mg/L in
group 1, 1.8 6 0.3 mg/L in group 2, and 2.9 6 0.5 mg/L in
group 3 and reached a peak concentration of 4.6 6 0.7 mg/L
in group 4 (P , 0.05 vs. groups 1–3; Fig. 1). The mean overnight serum bioactive GH concentration was 48 6 13 mg/L
in group 1, decreased from 39 6 8 mg/L in group 2 to a nadir
of 31 6 3 mg/L in group 3, and then increased 2-fold in
group 4 (64 6 15 mg/L; P , 0.05 vs. group 3; Fig. 1). The ratios
of bioactive GH to immunoreactive GH were 23 6 4, 23 6 2,
13 6 3, and 14 6 3 in groups 1, 2, 3, and 4, respectively (P ,
0.05, group 2 vs. groups 3 and 4).
E2 infusion study
To determine whether the changes we observed in serum
immunoreactive and bioactive GH concentrations throughout male pubertal maturation in the cross-sectional study
were related to increased circulating E2 concentrations, we
compared the effects of a 20-h infusion of saline vs. E2 on
serum GH and IGF-I concentrations in eight boys with stage
II and III puberty.
PUBERTY, E2, AND GH IN BOYS
2169
FIG. 1. Comparison of mean serum immunoreactive and bioactive GH, IGF-I,
and IGFBP-3 concentrations in 30 boys
in the cross-sectional study. Asterisks
represent statistical significance. Serum IGF-I and IGFBP-3 concentrations, shown in the upper panels,
showed a gradual increase with advancing puberty and peaked in group 4. The
serum immunoreactive GH concentration also increased gradually as pubertal maturation progressed and peaked
in group 4 (P , 0.05 vs. groups 1–3). The
serum bioactive GH concentration,
shown in the lower right panel, was
high in group 1, decreased to a nadir in
group 3, and increased significantly in
group 4 (P , 0.05 vs. group 3).
TABLE 4. Effect of E2 infusion on LH, E2, and T concentrations
Infusion
LH (IU/L)
E2 (pmol/L)
T (nmol/L)
Saline
E2
5.0 6 0.9
22.4 6 4.0
6.2 6 1.7
2.3 6 0.6a
81.0 6 26a
3.8 6 1.4b
Data are given as the mean 6
a
P , 0.01 vs. saline infusion.
b
P , 0.05 vs. saline infusion.
SE.
Mean overnight serum LH, E2, and T concentrations. The effectiveness of the E2 infusion was assessed by measurement of
E2, T, and LH concentrations during saline and E2 infusions.
The mean overnight serum E2 concentration increased significantly from 22 6 4 pmol/L during saline infusion to 81 6
26 pmol/L during E2 infusion (P 5 0.032), whereas the mean
serum LH and T concentrations decreased about 2-fold during the E2 infusion compared to those during the saline
infusion (Table 4).
Overnight GH pulse frequency and amplitude, mean serum immunoreactive and bioactive GH and IGF-I concentrations. The
mean overnight serum GH concentration determined by immunoassay was 6.6 6 1.4 mg/L during saline infusion and
9.7 6 2.1 mg/L during E2 infusion (P 5 0.16). The mean
amplitude of the first nocturnal GH peak increased 1.6-fold
from 26.4 6 2.4 mg/L during saline infusion to 42.8 6 9.0
mg/L during E2 infusion, but the difference was not significant (P 5 0.132). Mean overnight GH pulse frequency
(0.39 6 0.01 vs. 0.39 6 0.04 pulses/boyzh during saline and
E2 infusions, respectively) and pulse amplitude (17.8 6 4 and
14.5 6 1.8 mg/L during saline and E2 infusion, respectively)
did not change during E2 infusion.
Individual and mean data representing the effect of E2
infusion on immunoreactive and bioactive GH and IGF-I
concentrations are shown in Fig. 2. The mean overnight serum bioactive GH concentration decreased from 48 6 10 to
16 6 3.0 mg/mL during saline and E2 infusions, respectively
(P 5 0.0487). Similarly, the mean serum IGF-I concentration
decreased from 116 6 17 mg/L during saline infusion to 93 6
15 mg/L during E2 infusion (P 5 0.021).
Discussion
Increased linear growth during puberty occurs coincidentally with an increase in the mean serum GH concentration
and GH pulse amplitude (1–7). It has been thought that sex
steroids and, in particular, E2 increase GH secretion (31), yet
a direct relationship among E2, serum GH, and pubertal
growth has not been established even in thorough longitudinal studies in boys (32). We hypothesized that the isoform
profile of secreted GH might change in the face of rising sex
steroid concentrations at puberty, such that E2 might increase
the production of a highly bioactive species of GH with
limited immunoactivity. This hypothesis was examined in a
cross-sectional study of serum GH bioactivity in boys across
pubertal transition. Serum GH bioactivity in these boys increases abruptly between early and mid- to late puberty, but
the ratio of bioactive to immunoreactive GH concentrations
suggests that pubertal GH secretion is not characterized by
a secretion of GH isoforms with high biological potency. It
is of interest that serum bioactive GH concentrations are
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CEMEROGLU ET AL.
FIG. 2. Individual (scatter graph) and mean (bar graph) data of eight
boys during saline and E2 infusions. The serum immunoreactive GH
concentration increased in four boys, decreased in three boys, and did
not change in one boy during E2 infusion, and the mean immunoreactive GH concentration did not increase significantly during E2 infusion compared to that during saline infusion. Bioactive GH and
IGF-I concentrations decreased significantly during E2 infusion compared to those during saline infusion.
relatively greater in prepubertal boys with bone ages of 7 yr
or less and decrease to a nadir in early puberty. This tendency
of serum GH bioactivity to decline with age parallels the
reported decline in growth velocity with advancing age in
prepubertal boys, which reaches a nadir at 10 –11 yr when
pubertal signs first begin to appear (33). At this same time,
the serum IGF-I concentration, another biological marker of
GH activity, increases. Although serum IGF-I concentrations
are not governed solely by GH, if the decline in GH bioactivity preceding the pubertal growth spurt is borne out in
additional studies, then the current views regarding the interrelationship among GH, IGF-I, and growth will require
reexamination.
The overall complexity of the relationship among serum
GH, IGF-I, and E2 is highlighted by the unexpected results
obtained when E2 was infused in early to midpubertal boys.
We had expected that E2, if it had an effect, would increase
the serum GH concentration determined by immuno- and
bioassays. Instead, the serum GH concentration determined
by immunoassay was constant over the 20-h infusion period,
but serum GH bioactivity decreased by 67%, and that of IGF-I
decreased by 20%. The reason for the acute decline in serum
GH bioactivity is unclear. Serum E2 concentrations achieved
by the infusions were well within the normal concentration
range of adult men (,37 to 210 pmol/L) (26), but were twice
the concentrations of mid- to late pubertal boys in our cross-
sectional study. E2 infusion also suppressed serum T concentrations to values similar to those in the early pubertal
boys in our cross-sectional study, the same boys who exhibited the lowest serum bioactive GH concentrations. This
raises the intriguing possibility that the androgen, rather
than the estrogen, concentration in boys governs GH secretion, plasma processing, or GH clearance in such a way to
enhance GH bioactivity. Borski et al. showed in ovariectomized rats that chronic dihydrotestosterone treatment increases pituitary GH stores and circulating IGF-I levels and
decreases circulating GH levels, whereas E2 treatment has the
opposite effect (34). Thus, the serum concentration of E2
relative to that of T might be an important factor for the net
effect on the GH axis. We have shown in another study that
chronic E2 treatment in pubertal aged girls with gonadal
dysgenesis leads to a significant increase in serum GH concentrations determined by immuno- and bioassays (35).
These observations suggest that there may be sex differences
in the control of GH secretion and in the response of the GH
axis to E2 exposure during pubertal maturation and that
acute and chronic E2 exposures have different effects on
serum GH bioactivity. An initial decline in bioactivity with
short term exposure to E2, as seen in early pubertal boys of
our cross-sectional study, may be followed by an increase in
GH bioactivity with prolonged exposure. Alternatively,
there may be other factors in serum besides sex steroids that
affect the GH axis during pubertal maturation.
Acute E2 infusion results in a small, but significant, decrease in the serum IGF-I concentration. In a similar study,
a 4-day infusion of E2 in pubertal boys either did not change
or increased the serum IGF-I concentration (36). These conflicting results regarding the response of the serum IGF-I
concentration to E2 infusion may be due to differences in the
duration of sex steroid exposure. The acute decrease in the
IGF-I concentration may be related to either E2-mediated
changes in synthesis, as observed in liver (34, 37), or its
increased clearance from the circulation.
In this study we have shown that serum immunoreactive
and bioactive GH concentrations increase during late puberty in concert with an increase in T and E2 concentrations,
but the ratio of bioactive to immunoreactive GH concentrations suggests that pubertal growth in boys is not associated
with a shift in GH secretion to isoforms with high biological
potency. The relative importance of E2 vs. T on GH secretion
during pubertal maturation is still unclear. Acute E2 infusion
does not alter the serum immunoreactive GH concentration,
but serum IGF-I and bioactive GH concentrations decrease,
paralleling the decrease in the T concentration, suggesting
that the balance between T and E2 concentrations may be
important for GH secretion in males. Alternatively, there
may be other factors in the serum besides sex steroids that
increase during pubertal maturation and cause the changes
seen in GH and IGF-I secretion and the linear growth rate.
Acknowledgments
The authors thank Mrs. Maria Borondy and Mrs. Alice Rolfes-Curl for
their expert technical assistance, and Dr. Nancy J. Hopwood for her
helpful comments.
PUBERTY, E2, AND GH IN BOYS
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