Where in Fetal Life Are Androgen Receptors Expressed? 199
target receptors, metabolism, degradation, excretion, and many others.
The natural homeostasis of hormonal levels during a fetal life involves the
ability of the specific glands throughout prenatal development to precisely
regulate the hormonal levels by interactions with their natural targets. These
interactions, most often by negative feedback of a hormone through its receptor
in the original target brain and the rest of the fetal body, determine the best
outcome for a normotypic offspring. The finely tuned interplay keeps the levels
of any hormone within a physiologically relevant range to be most effective.
Excursions outside of that range to elevated or depressed levels for any
extended period can result in dysfunction in brain development (along with
other organs and the rest of the fetal body). A prime example of an unbalanced
hormone and its adverse outcome is the thyroid system: normal levels of
the thyroid hormones are needed for appropriate metabolic health.
Hyperthyroidism is associated with a range of symptoms due to elevated
metabolism, whereas hypothyroidism, with a very different disease phenotype,
results from depressed hormone levels (Figures 7.7 and 7.8).
Where in Fetal Life Are Androgen Receptors Expressed?
Androgen receptors (ARs) belong to the super family of ligand‐responsive
transcription regulators, which includes retinoic acid receptors, thyroid hor
mone receptors, and several steroid hormone receptors. Androgens have a
great variety of effects on many target tissues [102,103]. They induce the devel
opment and physiological function of male accessory sex organs, such as the
prostate and seminal vesicles, and later in life they control the functional activ
ity of target tissues. Androgen action in these organs and tissues is believed to
be mediated by ARs. Using immunohistochemical techniques, ARs have been
clearly demonstrated in nearly all human adult tissues [3], and in fetal tissues
from second and third trimester gestation, suggesting that ARs are involved in
early development [4], Figure 5.2. Analyses of AR expression in a variety of extra‐
genital tissues during weeks 8–12 of gestation revealed expression in the thymus
gland, bronchial epithelium of the lungs, and in cardiac valves. AR expression
was absent in the kidneys, adrenal glands, liver, and bowel. The study suggested
an important role of AR in organogenesis. Of note, the thymus is a primary
immune organ and an essential part of the adaptive immune defense system. In
human fetuses, the first lymphocytes in the human thymus primordium appear
around 8 weeks of gestation. In the thymus, lymphocytes begin to proliferate in
the epithelial stroma, under the influence of various thymic hormones that
induce stimulation, proliferation, and differentiation, and become competent
T lymphocytes by weeks 14–15 of gestation. This is the period during which
thymocytes go through a process called “clonal selection” and any thymocyte
that can recognize self‐antigen is destroyed. A major implication of these
