ACTH Stimulation and G Protein

Age Range:6 - 60
Start Date:July 2005
Contact:Kelly J Seiler, MD

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G Protein Expression in Response to ACTH Stimulation Testing

Males and females may exhibit different responses to testing of adrenal function. The
hormones responsible for controlling adrenal function are ACTH (adrenocorticotropic hormone
or corticotropin) and CRH (corticotropin-releasing hormone). Adrenal function is tested with
an ACTH stimulation test. ACTH stimulates the adrenal glands to produce cortisol. Cortisol
levels are measured, and a certain peak level indicates normal adrenal gland function.
Females may produce more cortisol in response to ACTH testing than males. This difference
may be due to certain proteins, called G proteins. The hormones controlling adrenal
function, ACTH and CRH, work through G proteins. Females may have more G proteins than males
allowing for the increased cortisol response to ACTH stimulation.

We speculate that:

1. There may be differences in adrenal responsiveness to ACTH stimulation testing between
healthy males and females.

2. ACTH and CRH induce their own function.

3. Sex differences in adrenal responsiveness to ACTH stimulation testing may be related to
sex differences in G protein expression.

In this study, cortisol, a hormone produced by the adrenal glands, will be measured before
and after the administration of ACTH.

This study will also measure G proteins. G proteins are found in the white blood cells.
White blood cells from females may have more active G proteins than white blood cells from
males. Sex differences may be augmented after exposure to ACTH.

Many nonsteroidal hormones work through G protein signal transducers. These heterotrimeric
signal transducers couple cell surface receptors to intracellular pathways, thus conveying
biologic effects. Most hormones that work via the stimulatory G protein, Gas, also exert
actions through a homologous stimulatory G protein, Gaq, suggesting that these pathways
exhibit redundancy. We have previously demonstrated sex differences in the expression of Gas
and Gaq. We have observed that female mice and humans display significantly higher levels of
mRNA and protein for the G protein, Gaq. We have also observed that estrogens induce
expression of Gaq mRNA and protein in female mice. In addition, preliminary studies in mice
demonstrate that both ACTH (adrenocorticotropic hormone or corticotropin) and CRH
(corticotropin-releasing hormone) induce Gq in immune cells and adrenal tissue in a sex
restricted fashion, i.e. females only.

ACTH and CRH are the two major hormones controlling adrenal function. Adrenal function can
be tested using a standard 1mcg synthetic ACTH stimulation test and measuring the production
of cortisol. We have observed that females exhibit a trend toward increased responsiveness
to ACTH stimulation than males. We speculate that sex differences in cortisol responsiveness
to ACTH exist, and that these differences will correlate with sex differences in the
expression or induction of the G proteins, Gaq or Gas.

We propose to determine whether healthy female subjects undergoing low-dose ACTH stimulation
exhibit altered levels of Gaq or Gas mRNA and protein and cortisol levels compared with male
subjects undergoing the same provocative testing. This study may have implications for the
interpretation of provocative ACTH testing.

Inclusion Criteria:

Healthy males and females aged 6-60

Exclusion Criteria:

known medical condition, use of inhaled, topical, or oral steroids, use of oral
contraceptive pills or hormone replacement, menopause, pregnancy
We found this trial at
2401 Gillham Rd
Kansas City, Missouri 64108
(816) 234-3000
Children's Mercy Hospital Children's Mercy Hospitals and Clinics continues redefining pediatric medicine throughout the Midwest...
Kansas City, MO
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