Impairments of Endocrine Functions: Causes and Consequences - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 190

In vertebrates, the main hormones are those released in the hypothalamus that stimulate
pituitary activity, and then stimulate thyroid, adrenal, gonadal, and pancreatic activity.
The THs contribute to the regulation of metabolism, growth and development, behavior,
and puberty. The corticosteroid hormones and catecholamines secreted in adrenal glands
also intervene in metabolism and behavior. Insulin and glucagon secreted in the pan-
creas regulate blood sugar levels. The sex steroid hormones (androgens and estrogens)
produced in the gonads regulate development and growth, reproduction, immunity, onset
of puberty, and behavior. The production and circulating levels of hormones are controlled
by means of negative feedback processes.
The endocrine system is important for the control and regulation of all major functions
and processes of the body: energy control, reproduction, immunity, behavior, growth, and
development.
8.2.2 Mechanisms of Endocrine Disruption: Principle of Lock and Key
8.2.2.1 Mechanisms of Disruption
Potential sites of toxic action of pollutants on the endocrine system in fish and other organ-
isms concern (1) the perception of environmental stimuli by the nervous system, the syn-
thesis and release of hypothalamic hormones (RH/IH); (2) the synthesis and release of
hypophyseal hormones [GTH, ACTH, thyroid stimulating hormone (TSH)]; (3) the response
of endocrine glands under the control of the hypophysis (gonads, interrenal tissue, thy-
roid gland) and other glands (e.g., endocrine pancreas); (4) the synthesis and release of
hormones by other endocrine glands; (5) the response of target organs to hormones; and
(6) the metabolism and elimination of hormones by excretory organs (Hontela 2000).
Some chemicals can act on the endocrine system to disturb the homeostatic mechanisms
of the body or to initiate processes at abnormal times in the life cycle. First, they may
mimic the biological activity of a hormone by binding to a cellular receptor, leading to an
unwarranted response by initiating the cell's normal response to the naturally occurring
hormone at the wrong time or to an excessive extent (agonistic effect). Second, they may
bind to the receptor but not activate it. Instead, the presence of the chemical on the receptor
will prevent binding of the natural hormone (antagonistic effect). Third, they may bind to
transport proteins in the blood, thus altering the amounts of natural hormones present in
the circulation. Fourth, they may interfere with the metabolic processes in the body, affect-
ing the synthesis or breakdown rates of the natural hormones.
The normal mechanism of the action of hormones, for example, steroid hormones,
includes three stages. After hormones bind to the receptor, this couple is internalized in
the nucleus, where it can interact with other proteins to bind to specific promoter regions
of DNA (Figure 8.1). The genes under hormonal regulation possess in their promoter
region an element of response in the hormone/receiver (RRE) complex. The binding of the
complex on this element of response is going to provoke the expression of the gene until
then silent (Figure 8.1). The endocrine disrupter can exert its toxic action either by prevent-
ing or modifying binding to the receptor, or by settling on the promoter region of the gene,
for example, by methylation.
Endocrine disruptors can bind to the hormonal receptor, and the hormonal signal may
be enhanced or decreased (Figure 8.2). This is an example of lock and key. As a rule, a
single key can match a given lock. But in reality, several keys can enter the lock, making it
turn or blocking it. This is all the more true as the number of locks (hormonal receptors)
and keys (EDCs) is multiplied.