Hormones as Messengers and Regulators — Feedback Control

Beyond understanding how a single hormone molecule acts on a single target cell, it is equally important to understand how the endocrine system as a whole manages to keep the level of each circulating hormone within an appropriate physiological range, neither too high nor too low, over the course of hours, days and years. Hormones function, in the fullest sense, both as chemical messengers, carrying information from a secreting gland to distant target tissues, and as regulators, adjusting the ongoing activity of those target tissues in line with the body's current needs — and this regulatory role depends critically on the endocrine system's ability to sense its own hormone output and correct any departure from the appropriate level.

The great majority of hormonal control loops in the body achieve this self-correction through negative feedback, in which the hormone (or a downstream product of its action) produced at the end of a control chain acts back on the gland or glands that originally stimulated its release, damping down further stimulation once a sufficient amount of hormone is present in the blood — functioning, in effect, exactly like a household thermostat that switches a heater off once the room has reached the desired temperature. The hypothalamus-pituitary-thyroid axis provides a clear illustration: the hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH), which in turn stimulates the thyroid gland to secrete T3 and T4; but once circulating T3/T4 levels rise sufficiently, they act back directly on both the hypothalamus and the anterior pituitary, suppressing further TRH and TSH secretion and so preventing thyroid hormone level from continuing to climb once an adequate level has been reached. Essentially the same three-tier pattern — hypothalamus, anterior pituitary, and a peripheral target gland, with the target gland's own hormone output feeding back to restrain the two tiers above it — is repeated in the hypothalamus-pituitary-adrenal axis (regulating cortisol) and the hypothalamus-pituitary-gonadal axis (regulating testosterone, estrogen and progesterone), making negative feedback via such an axis the single most common organisational pattern across the entire endocrine system. The PTH-calcitonin system regulating blood calcium, and the insulin-glucagon system regulating blood glucose, described earlier in this chapter, work by a closely related logic, even though they do not involve a hypothalamus-pituitary axis as such: in each case, a departure of the regulated variable (blood calcium, blood glucose) from its normal level itself directly triggers the corrective hormonal response, which then subsides again once the variable has been restored to normal. …