Chapter 13. Endocrine system I
The hypothalamus and pituitary
LEARNING OBJECTIVES
At the end of this chapter, the reader should be able to:
• explain the terms endocrine, paracrine and autocrine hormones
• describe the hypothalamus–pituitary axis
• describe the anatomy of the pituitary stalk and the two main pituitary lobes
• give the names, actions and some uses of the hypothalamic releasing and inhibiting hormones
• give the names, actions and some uses of the anterior lobe hormones
• list the posterior lobe hormones and what their main actions are
• be aware of the role of the hypothalamus and the hormone leptin in appetite control
Hormones
The endocrine or ductless glands are organs or small islands of tissue in various parts of the body. Each gland secretes a substance – or, in some cases, several substances – called hormones. These are released from the gland and may enter the bloodstream and circulate through the body and act on distant organs or tissues (called an endocrine action); act on neighbouring cells (called a paracrine action); act on the cells that released them (called an autocrine action; see Fig. 13.1).
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| Figure 13.1 Actions of endocrine organs. |
Some hormones may have two or even all three types of action. Their speed of action is variable; the effects of some hormones are seen almost immediately after release (e.g. insulin), whereas others may take hours or even days to show their effects (e.g. estrogens). After release, these hormones act upon a receptor mechanism in the organ or organs they influence, thus producing their specific actions. The actions of the various hormones differ widely: one group is concerned with metabolic processes, another with secondary sexual characteristics, and so on. Sometimes, a hormone will act on another endocrine gland and stimulate it to produce a further hormone, a mechanism crucial in the control of the release of endocrine hormones such as cortisol and the sex hormones by the brain and pituitary gland.
Many of these hormones have been isolated and their structure determined. This has made it possible to prepare synthetically either the hormones or analogues. which are sometimes more active and more stable than the hormones themselves.
Classification of endocrine glands
For purposes of study, the endocrine glands can be divided roughly into three groups:
Classification note
• the pituitary gland, which secretes hormones that exercise a controlling influence over much of the rest of the endocrine system, and which, in turn, is largely controlled by the hypothalamus of the brain
• endocrine glands affecting metabolism
• endocrine glands affecting the reproductive system.
Classification note
The above classification is purely for the purpose of facilitating chapter division of this section of the book. It can be argued with much justification that since the pituitary gland controls most other glands, it affects both metabolism and reproduction, which of course it does.
This chapter deals with the hypothalamus–pituitary axis, the hormones of the axis and the drugs derived from them.
The hypothalamus–pituitary axis
The pituitary is a small endocrine gland attached to the brain by a stalk and lying, almost surrounded by bone, in the base of the skull. It consists of anterior and posterior lobes. In spite of its small size, it is of great importance. It secretes a number of hormones that affect not only various processes in the body but also the activity of most of the other endocrine glands. It is of interest that the activity of the pituitary itself is influenced by other hormones, both from the brain and from other glands in the body. Those other hormones regulate secretion of pituitary hormones through feedback mechanisms (see below).
The release of the pituitary hormones of the anterior lobe is a complex function and for many of them there is a specific releasing hormone, which is produced in the brain, specifically in the hypothalamus. Some of the hypothalamic hormones do not stimulate but inhibit release of anterior lobe hormones instead (see Table 13.1). The anterior pituitary hormones in turn stimulate the release of hormones from the endocrine glands. Those hormones exert their various effects on the body, and also travel to the brain and to the pituitary gland, where they either stimulate or inhibit the release of releasing hormones and/or the pituitary gland hormones. These regulatory actions of the endocrine hormones are called feedback effects, and are of great importance in the design of several drugs, including the contraceptive pill (see p. 217).
| Hypothalamic releasing or inhibitory hormone | Anterior lobe hormone |
|---|---|
| Corticotrophin-releasing hormone (CRH) | Adrenocorticotrophic hormone (ACTH; corticotrophin) |
| Gonadotrophin-releasing hormone (GnRH) | Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) |
| Thyrotrophin-releasing hormone (TRH) | Thyroid-stimulating hormone (TSH; thyrotrophin) |
| Growth hormone-releasing hormone (GHRH; somatorelin) | Growth hormone (GH) |
| Growth hormone-inhibitory hormone (GHIH; somatostatin) | Growth hormone (GH) |
| Dopamine (DA) (inhibits release of prolactin), TRH, prolactin-releasing peptide (PRP) (stimulates release of prolactin) | Prolactin |
The pituitary stalk
The pituitary is connected to the hypothalamus of the brain by a stalk. The stalk contains nerves that connect the hypothalamus to the posterior lobe, and blood vessels that connect the hypothalamus to the anterior lobe. The blood vessels are called the portal system because they carry hormones from the hypothalamus to the pituitary. The nerves to the posterior lobe carry both electrical signals and the hormones oxytocin and vasopressin (see below), which are stored in the posterior pituitary until release into the general circulation.
Control of pituitary hormone release
There are two groups of hormones:
• anterior lobe hormones
• posterior lobe hormones.
Control of anterior lobe hormone release
The release of anterior lobe hormones is governed largely by the hypothalamic releasing hormones. The hypothalamic hormones and the anterior lobe hormones they control are shown in Table 13.1.
The hypothalamic releasing and inhibitory hormones are
• CRH
• GnRH
• TRH
• GHRH (somatorelin)
• GHIH (somatostatin)
• dopamine.
These hormones, with the exception of dopamine, are all peptides and are important because they or drugs derived from them are used both therapeutically and diagnostically.
CRH
CRH is corticotrophin-releasing hormone. It is a peptide synthesized in the hypothalamus and it causes the release of adrenocorticotrophic hormone (ACTH) from the anterior pituitary. It is used clinically mainly as a diagnostic tool to test the ability of the pituitary to release ACTH. Cortisol and the synthetic steroids such as prednisolone inhibit its release by a negative feedback mechanism. CRH is now also known to be important in the control of food intake and the problem of obesity, and drugs are being sought to modulate its action in the treatment of obesity, which is a major and growing problem in the UK.
Safety note
Safety note
Patients on steroids such as prednisolone must be weaned off them gradually. This is because prolonged use of prednisolone completely suppresses the CRH–ACTH–cortisol system, which normally protects the patient from stress and is important in glucose metabolism. Gradual reduction in prednisolone allows cortisol levels to rise again (see also below).
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