The Endocrine System

As with the nervous system, the basic functions of the endocrine system are communication and regulation. The classic endocrine system consists of a group of ductless glands that secrete hormones (chemical messengers that function in extremely small concentrations). The hormones circulate throughout the body to bring about physiologic responses. However, this classic description does not account for other types of chemical messengers involved in other types of cell-to-cell communication and regulation. For example, paracrine agents produce a paracrine effect – a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells.

Approximate location of classic endocrine glands (Source: R.D. Frandson, W.L. Wilke, and A.D. Fails; Anatomy and Physiology of Farm Animals; 7th edition)

Hormone Receptors

Only specific populations of cells are responsive to a given hormone. Target organ refers to the tissue whose cells will be affected by a particular hormone. Some hormones have multiple target organs because they affect cells at multiple locations. Among the target organs for insulin are, for instance, both skeletal muscle and the liver.

Because they contain specific receptors capable of binding or forming a chemical union with the hormone, cells within target organs can recognise and respond to a specific hormone. These cellular receptors may be components of the cell membrane with an extracellular fluid-exposed binding site, or they may be in the cytoplasm or nucleus of cells. In either case, for a cell to respond to a specific hormone, a receptor for that hormone must be present.

Under certain conditions, the presence and number of receptors within target cells may change. This is one method for regulating the biological effect of a given hormone. For instance, the reproductive hormone oestrogen causes a rise in oxytocin receptors in the smooth muscle of the uterus shortly before birth (parturition). The increase in oxytocin receptors prepares the uterus so that, when released during labour, oxytocin can stimulate uterine contractions. Without the increase in oxytocin receptors stimulated by oestrogen, the release of oxytocin alone would not be sufficient for normal parturition. Up-regulation refers to an increase in receptors on target cells, while down-regulation refers to a decrease.

The major endocrine glands, the hormones they secrete, and their primary action on their target tissue or organ (Source: R.D. Frandson, W.L. Wilke, and A.D. Fails; Anatomy and Physiology of Farm Animals; 7^th edition).

Endocrine Gland	Hormone	Action (target tissue or organ)
Hypothalamus	Corticotropin-releasing hormone(CRH).	Stimulates corticotrophin (ACTH) release from the anterior pituitary (adenohypophysis).
	Gonadotropin-releasing hormone (GnRH).	Stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release from the anterior pituitary.
	Growth hormone-releasing hormone (GHRH).	Stimulates growth hormone (GH) release from the anterior pituitary.
	Growth hormone-inhibiting hormone (GHIH).	Inhibits growth hormone (GH) release from the anterior pituitary.
	Thyrotrophin-releasing hormone (TRH).	Stimulates thyrotrophin (TSH) release from the anterior pituitary.
	Dopamine.	Inhibits prolactin (PRL) release from the anterior pituitary.
	Oxytocin and antidiuretic hormone are synthesized in the hypothalamus; stored and released from the posterior pituitary (neurohypophysis).
Adenohypophysis (anterior pituitary)	ACTH	Stimulates cortical development and glucocorticoid release from the adrenal cortex.
	FSH	Stimulates follicular development in the ovaries and sperm development in the testes.
	LH	Stimulates ovulation, development of the corpus luteum in the ovary, secretion by the corpus luteum, and secretion of androgens in the testes.
	GH	Promotes growth in immature animals. Has metabolic effects on carbohydrate, lipid, and protein metabolism in adult animals.
	TSH	Stimulates the release of thyroid hormones from the follicular cells of the thyroid gland.
	PRL	Promotes lactation in the mammary gland, and maternal behaviour from the central nervous system.
Neurohypophysis (posterior pituitary)	Oxytocin	Stimulates uterine contraction and milk let- down in the uterus and mammary glands, respectively.
Neurohypophysis (posterior pituitary)	Antidiuretic hormone (ADH).	Conserves water and reduces urine volume in the kidneys. Constricts vessels to raise blood pressure in arterioles.
Adrenal cortex	Glucocorticoids.	Essential for normal stress response. Important roles in protein and carbohydrate metabolism in multiple organs including the liver.
Adrenal cortex	Mineralocorticoids (aldosterone).	Conserve sodium (Na) and eliminate potassium (K) in the kidneys.
Adrenal medulla	Epinephrine and norepinephrine.	Enhances sympathetic response to stress by actions on several organs.
Thyroid follicular cells	T₄ and T₃.	Increases oxygen consumption and adenosine triphosphate (ATP) generation in almost all cells.
Thyroid parafollicular cells	Calcitonin.	Promotes calcium retention in bone.
Parathyroid	Parathyroid hormone (PTH).	Promotes an increase in plasma calcium and a reduction in plasma phosphate in bones and the kidneys.
Pancreatic islets: β-cells	Insulin	Promotes glucose uptake, and protein and lipid synthesis by various tissues and organs, including skeletal muscle, liver, and adipose tissue.
Pancreatic islets: α-cells	Glucagon	Promotes glycogenolysis, and gluconeogenesis in the liver.

Negative and Positive Feedback Regulation

Assuming enough functional receptors are present, the biological effect of any hormone is directly proportional to the concentration of the hormone in body fluids that can bind to the receptors. This concentration is mainly determined by two factors:

The rate of hormone release from endocrine cells.
The rate of elimination from the body fluids.

The concentration is typically determined by the rate of release under normal conditions. Endocrine cells store peptide hormones and amines in secretory granules so that they are readily available for release. Steroid hormones cannot be stored and must be synthesised immediately before release.

The release and, consequently, the plasma concentration of most hormones are governed by negative feedback regulation. In this type of regulation, the rising levels of the hormone trigger a biological response that inhibits the release of additional hormones. For example, β-cells in the pancreatic islets are directly affected by the concentration of glucose in the body fluids. An increase in glucose concentration causes the β-cells to increase their release of insulin. One effect of insulin is to promote the uptake of glucose by skeletal muscle cells. As glucose is removed from the body fluids, the stimulus for insulin release is removed, which has a negative effect on insulin release. This negative feedback regulation of insulin release is a major determinant of a normal plasma concentration of glucose.

The regulation of insulin by changes in plasma glucose via negative feedback is a relatively straightforward feedback loop. The glucose component of plasma, which is regulated by the hormone insulin, has a direct effect on the cells that release insulin.

Nonetheless, negative feedback loops can be quite intricate and involve multiple organs. The hormones regulating reproduction in domestic animals and the hypothalamus, anterior pituitary gland, and gonads are involved in some of the more complex feedback loops.

Positive feedback regulation is a second type of feedback regulation that is much less common than negative feedback regulation. In this instance, the hormone induces a biological response that increases hormone release. This is an uncommon type of regulation, and it is not intended to maintain a stable or homeostatic level of an activity or a blood constituent. One of the few examples of this type of regulation is the connection between oxytocin release and cervical dilation. During parturition, an increase in oxytocin release is associated with cervical dilation, and oxytocin acts on the smooth muscle of the uterus to increase uterine contractions. During parturition, when the cervix dilates and oxytocin is released, the uterine contractions move the foetus out of the uterus through the cervix. This further dilates the cervix, increasing the stimulation for oxytocin secretion. The overall effect of a dilated cervix is the expulsion of the foetus.

Positive feedback regulation of oxytocin during parturition

Negative feedback loop of insulin release