The neuroendocrine system: What are the regulatory processes involved?

Hormones are chemical messengers that transmit information, regulate important metabolic

processes, and thereby control the interaction between the body’s organs. To ensure the

necessary fine-tuning, the body needs to control the synthesis and secretion of various hormones.

This central regulation is primarily achieved through interaction between the hypothalamus

and pituitary gland.

The hypothalamus is part of the diencephalon and processes information from the periphery

and higher brain centers. Therefore, it represents the highest regulatory center for the autonomic

nervous system and endocrine function. The hypothalamus is directly connected to the

pituitary gland, which has two distinguishing parts: the posterior pituitary, also called

the neurohypophysis, and the anterior pituitary, also termed the adenohypophysis. The posterior

pituitary is a functional, evolutionary, and anatomic part of the diencephalon. The hypothalamic

effector hormones ADH and oxytocin, are temporarily stored in the posterior pituitary and released

into the bloodstream when needed, where they’re transported directly to target organs.

In contrast, the anterior pituitary is an endocrine organ and not considered to be part

of the diencephalon. It’s connected to the hypothalamus through a portal vascular system.

The anterior pituitary produces two different types of hormones: tropic hormones, which

target peripheral endocrine glands and stimulate the production of effector hormones; and non-tropic

hormones, which exert a direct effect on target cells or organs. The hormones of the anterior

pituitary are transported via the bloodstream to their respective target organs: tropic

hormones to the thyroid gland, adrenal cortex, and gonads; and non-tropic hormones to the

liver and mammary glands.

Depending on the target organ or the effector hormone controlled by the interaction between

the hypothalamus and pituitary gland, there are five regulatory systems. These are termed

the neuroendocrine system or hypothalamic-pituitary axes.

Before we start to look at them in more detail, let’s first summarize their common active

principle. This will help you to remember the details of the various endocrine hormone

systems.

The hypothalamus produces regulatory hormones, that is, releasing hormones and inhibiting

hormones. Releasing hormones, which are often called liberins, stimulate the production

and secretion of anterior pituitary hormones. Inhibiting hormones, also termed statins,

inhibit the synthesis and release of anterior pituitary hormones. Regulatory hormones are

peptide hormones that are formed through proteolysis from precursors. In addition, tropic hormones

are also almost exclusively peptide hormones. They act on peripheral endocrine glands in

the body and stimulate the synthesis of effector hormones. These, in turn, belong to completely

different hormone classes and fulfill various functions in the body.

Effector hormones act via negative feedback mechanisms on the hypothalamic-pituitary system.

They inhibit both the secretion of tropic hormones in the anterior pituitary and releasing

hormones in the hypothalamus. This inhibition is termed long-loop feedback. The tropic hormones

of the anterior pituitary also have a similar inhibitory effect on the hypothalamus. This

negative feedback is called short-loop feedback. All negative feedback loops serve to maintain

hormonal balance.

Let’s first take an in-depth look at the hypothalamic-pituitary-thyroid axis. This

axis is also called the thyrotropic axis and is derived from the Greek word “thyreoidea”

meaning thyroid gland. The hypothalamic-pituitary-thyroid axis plays an important role in regulating

metabolism and growth. To achieve this, thyrotropin-releasing hormone, in short TRH, is secreted by the

hypothalamus. It leads to the release of TSH, thyroid-stimulating hormone, in the pituitary

gland, which acts directly on the thyroid gland, resulting in the secretion of the thyroid

hormones T3 and T4. These hormones are iodine-substituted derivatives of the amino acid tyrosine. T3

and T4 inhibit the release of hormones in the hypothalamus and the pituitary gland through

negative feedback. Another important regulatory element of the hypothalamus-pituitary-thyroid

axis is the inhibition of TRH and TSH secretion through somatostatin, which originates from

both the hypothalamus and pancreas. This connection enables hormonal adjustment that depends on

the varying food supply.

A similar situation also applies to the somatotropic axis through which the hypothalamus and pituitary

gland influence the processes in the liver. It plays an important role in anabolic metabolism

and cell growth. This stimulation is mediated by growth hormones, such as IGF, which are

produced in the liver. The stimulation of the release of IGF starts with the release

of growth hormone-releasing hormone, in short GHRH, in the hypothalamus. This stimulates

the release of growth hormone, in short GH, in the pituitary gland. GH then acts directly

on growth hormone synthesis in the liver. In turn, growth hormones inhibit the release

of GHRH and GH via the feedback loops. To ensure that the anabolic processes in the

body complement the food supply, there is also an inhibitory effect of somatostatin

and a stimulatory effect of ghrelin from the stomach.

The hypothalamic-pituitary-adrenal axis, which is seen as the body’s stress system, regulates

several important functions in the body. It primarily initiates a stress reaction and

also causes immunosuppression, and effects the balance of energy as well as mood. The

corticotropin-releasing hormone, in short CRH, and antidiuretic hormone, in short ADH,

are released in the hypothalamus. Together, CRH and ADH stimulate the release

of adrenocorticotropic hormone, in short ACTH, in the pituitary gland. ACTH promotes steroid

hormone production in the adrenal cortex, particularly glucocorticoids, whose primary

representative is cortisol. Cortisol, in turn, inhibits the release of hormones in the hypothalamus

and pituitary gland through negative feedback.

Through the hypothalamic-pituitary-gonadal axis, the hypothalamus and pituitary gland

also regulates hormonal secretion in the gonads, that is, the ovary and testes, respectively.

In the hypothalamus, gonadotropin-releasing hormone, also termed GnRH, is released. It

leads to the secretion of luteinizing hormone, in short LH, and follicle stimulating hormone,

in short FSH, from the pituitary gland. In men, LH stimulates the production of androgen,

whereas FSH stimulates spermatogenesis. In women, LH also stimulates androgen synthesis,

whereas FSH increases estrogen synthesis. The sex hormones also inhibit the secretion

of GnRH as well as FSH and LH. In addition, FSH stimulates the release of inhibin from

Sertoli cells located in the testes and from the granulosa cells of the ovaries. Following

their release, inhibins act primarily to inhibit FSH secretion.

The fifth and last axis of the neuroendocrine system primarily regulates milk production

in women during late pregnancy and lactation and is, therefore, known as the hypothalamic-pituitary-prolactin

axis. The hormone prolactin plays a central role in this feedback loop and is secreted

from the pituitary gland. Interestingly, prolactin is not only produced in women during pregnancy

but can also be found in men, although at a markedly lower concentration.

The hypothalamus stimulates prolactin secretion through various factors that are still somewhat

obscure and require further research. An important known factor is TRH, which was previously

mentioned as part of the hypothalamic-pituitary-thyroid axis. In addition, the hypothalamus can release

dopamine and thereby inhibit prolactin secretion. To initiate lactation, the combination of

prolactin and the estrogen produced by the adrenal cortex and ovaries acts on the mammary

glands.

Finally, let’s take another comparative look at the hormone axes. Although many different

biochemical factors play a role, there are some common points to remember:

The neuroendocrine system consists of five major hypothalamic-pituitary hormone axes,

whose names are derived from the corresponding endocrine target organ or effector hormones.

The hypothalamus stimulates the release of hormones from the anterior pituitary by secreting

releasing hormones. Their abbreviated name usually ends with RH. In addition, the hypothalamus

produces inhibiting hormones such as dopamine, which inhibits the production of prolactin

from the pituitary gland, and somatostatin, which inhibits the secretion of both TRH and

GHRH. The pituitary gland secretes four tropic hormones,

FSH, LH, ACTH, and TSH, as well as two non-tropic hormones, prolactin and GH. The anterior pituitary

hormones are transported via the bloodstream either to peripheral endocrine glands or directly

to their target organ where they exert their stimulatory effect.

All effector hormones have an inhibitory effect on hormone release from the hypothalamus and

the pituitary gland and act as a trigger for negative feedback. This leads to a hormonal

balance in the different feedback loops. Each of the hypothalamic-pituitary axes is affected

by additional factors from different organ systems. We’ve presented several important

ones in the overview. Further information can be found in our library.

If you’d like to test your knowledge on the various axes of the neuroendocrine system,

then stay put for the quiz.