Medical Endocrinology 8

Medical Endocrinology 8



Medical Endocrinology 8
Control of Secretion by the Anterior Pituitary
Secretion of anterior pituitary hormones is regulated in two ways.
First, neurosecretory cells in the hypothalamus secrete five releasing hormones, which stimulate secretion of anterior pituitary hormones, and two inhibiting hormones, which suppress secretion of anterior pituitary hormones .
Second, negative feedback in the form of hormones released by target glands decreases secretions of three types of anterior pituitary cells (Figure ). In such negative feedback loops, the secretory activity of thyrotrophs, gonadotrophs, and corticotrophs decreases when blood levels of their target gland hormones rise.
For example, adrenocorticotropic hormone (ACTH) stimulates the cortex of the adrenal gland to secrete glucocorticoids, mainly cortisol. In turn, an elevated blood level of cortisol decreases secretion of both corticotropin and corticotropin-releasing hormone (CRH) by suppressing the activity of the anterior pituitary corticotrophs and hypothalamic neurosecretory cells.

Figure: Negative feedback regulation of hypothalamic neurosecretory cells and anterior pituitary corticotrophs. Solid green arrows show stimulation of secretions; dashed red lines show inhibition of secretion via negative feedback.
Cortisol secreted by the adrenal cortex suppresses secretion of CRH and ACTH.

Human Growth Hormone and Insulinlike Growth Factors
Somatotrophs are the most numerous cells in the anterior pituitary, and Human Growth Hormone (hGH) is the most plentiful anterior pituitary hormone.

The main function of hGH is to promote synthesis and secretion of small protein hormones called Insulinlike Growth Factors (IGFs) or Somatomedins. In response to human growth hormone, cells in the liver, skeletal muscles, cartilage, bones, and other tissues secrete IGFs, which may either enter the bloodstream from the liver or act locally in other tissues as autocrines or paracrines.

The functions of IGFs include the following:

1. IGFs cause cells to grow and multiply by increasing uptake of amino acids into cells and accelerating protein synthesis.
IGFs also decrease the breakdown of proteins and the use of amino acids for ATP production. Due to these effects of the IGFs, human growth hormone increases the growth rate of the skeleton and skeletal muscles during childhood and the teenage years. In adults, human growth hormone and IGFs help maintain the mass of muscles and bones and promote healing of injuries and tissue repair.

2. IGFs also enhance lipolysis in adipose tissue, which results in increased use of the released fatty acids for ATP production by body cells.

3. In addition to affecting protein and lipid metabolism, human growth hormone and IGFs influence carbohydrate metabolism by decreasing glucose uptake, which decreases the use of glucose for ATP production by most body cells. This action spares glucose so that it is available to neurons for ATP production in times of glucose scarcity. IGFs and human growth hormone may also stimulate liver cells to release glucose into the blood.

Somatotrophs in the anterior pituitary release bursts of human growth hormone every few hours, especially during sleep. Their secretory activity is controlled mainly by two hypothalamic hormones:

(1) growth hormone–releasing hormone (GHRH) promotes secretion of human growth hormone, and

(2) growth hormone–inhibiting hormone (GHIH) suppresses it. A major regulator of GHRH and GHIH secretion is the blood glucose level (Figure ):

Figure : Effects of human growth hormone (hGH) and insulinlike growth factors (IGFs). Dashed lines indicate inhibition.
Secretion of hGH is stimulated by growth hormone–- releasing hormone (GHRH) and inhibited by growth hormone–inhibiting hormone (GHIH).

1. Hypoglycemia (h?¯ _-po-gl?¯-SE¯ -me¯ -a), an abnormally low blood glucose concentration, stimulates the hypothalamus to secrete GHRH, which flows toward the anterior pituitary in the hypophyseal portal veins.
2. Upon reaching the anterior pituitary, GHRH stimulates somatotrophs to release human growth hormone.
3. Human growth hormone stimulates secretion of insulinlike growth factors, which speed up breakdown of liver glycogen into glucose, causing glucose to enter the blood more rapidly.
4. As a result, blood glucose rises to the normal level (about 90 mg/100 mL of blood plasma).
5. An increase in blood glucose above the normal level inhibits release of GHRH.
6. Hyperglycemia (h?¯ _-per-gl?¯-SEE¯ -me¯ -a), an abnormally high blood glucose concentration, stimulates the hypothalamus to secrete GHIH (while inhibiting the secretion of GHRH).
7. Upon reaching the anterior pituitary in portal blood, GHIH inhibits secretion of human growth hormone by somatotrophs.
8. A low level of human growth hormone and IGFs slows breakdown of glycogen in the liver, and glucose is released into the blood more slowly.
9. Blood glucose falls to the normal level.
10. A decrease in blood glucose below the normal level (hypoglycemia) inhibits release of GHIH.

Other stimuli that promote secretion of human growth hormone include decreased fatty acids and increased amino acids in the blood; deep sleep (stages 3 and 4 of non-rapid eye movement sleep); increased activity of the sympathetic division of the autonomic nervous system, such as might occur with stress or vigorous physical exercise; and other hormones, including glucagon, estrogens, cortisol, and insulin. Factors that
inhibit human growth hormone secretion are increased levels of fatty acids and decreased levels of amino acids in the blood; rapid eye movement sleep; emotional deprivation; obesity; low levels of thyroid hormones; and human growth hormone itself (through negative feedback).


Clinical Connection: Diabetogenic Effect of hGH
One symptom of excess human growth hormone (hGH) is hyperglycemia. Persistent hyperglycemia in turn stimulates the pancreas to secrete insulin continually. Such excessive stimulation, if it lasts for weeks or months, may cause “beta-cell burnout,” a greatly decreased capacity of pancreatic beta cells to synthesize and secrete insulin. Thus, excess secretion of human growth hormone may have a Diabetogenic Effect; that is, it causes Diabetes Mellitus (lack of insulin activity).
Thank You
Prof. Dr. Sa ad Merza Alaraji