Endocrine Physiology: 01-27-12 (Otey)

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TRANSPORTATION OF HORMONES IN THE CIRCULATION:

Most amines and peptide hormone circulate freely in plasma unbound to any carrier proteins because they are usually ___ and freely ___.

Two exceptions to this rule are ___ hormone and ___ growth factor, which circulate in plasma bound to specific binding proteins.

charged, soluble

growth, insulin-like

TRANSPORTATION OF HORMONES IN THE CIRCULATION:

___ and ___ hormones are bound by carrier proteins that have saturable, high affinity binding sites for the hormones they carry (ex: thyroid hormone binding globulin).

Binding proteins ___ hormone access to target cells and ___ steroids from metabolism and degradation.

Steroids, thyroid

limit, protect

TRANSPORTATION OF HORMONES IN THE CIRCULATION:

Binding of hormones to carrier proteins ___ the half-life of the hormone in the circulation. The half-life of a hormone is defined as the time it takes for the concentration of a hormone to decline to half of a ___ steady state concentration.

In general: The stronger the binding of a carrier protein to a hormone, the ___ the clearance rate of the hormone and the ___ the hormone half-life.

Average half-lives of hormones in plasma:
• amines 2-3 min
• T3 ~18 hr
• T4 ~7 days
• steroids 4 - 120 minutes
• polypeptides 4 - 30 min

increases, starting

slower, longer

TRANSPORTATION OF HORMONES IN THE CIRCULATION:

The rate of hormone disposal is important clinically because:

If hormone replacement is required due to hormone deficiency, the frequency of administration of hormone will be determined by how rapidly the hormone is __ from the circulation.

Pathologically high circulating hormone concentrations could result from an inability to ___ hormone from the circulation (e.g. kidney disease can result in high levels of many circulating hormones).

removed

remove

The pituitary gland (also called the hypophysis) lies at the ___ of the brain and is connected to the hypothalamus by the pituitary ___.

The pituitary gland has two parts that are distinguished morphologically and functionally:

1. The adenohypophysis arises as a outgrowth of ___ ___ (adeno = glandular or epithelial).

2. The neurohypophysis receives its name because it is embryologically derived from the developing ___.

base, stalk

pharyngeal epithelium

hypothalamus

Because the pituitary is involved in regulating processes as diverse as reproduction, growth, metabolism, temperature, and our response to stress, the pituitary is often called the "___ gland".

Some pituitary hormones influence cellular processes ___, while others act by stimulating other ___ glands to increase or decrease the secretion of a second hormone.

master

directly, endocrine

6 major hormones of anterior pituitary:

1. ___-Stimulates adrenal cortex growth, stimulates cortisol production and release

2. ___-Stimulates growth of thyroid gland, stimulates thyroid hormone production and release

3. ___-Stimulates ovarian follicle development in females and spermatogenesis in males

4. ___-Causes ovulation and production of the corpus luteum in females, stimulates sex steroid synthesis in males and females

5. ___-Stimulates milk production by lactating mammary glands

6. ___-Stimulates body growth, organ growth and regulates metabolism

1. Adrenocorticotropin (ACTH)

2. Thyrotropin; thyroid stimulating hormone (TSH)

3. Follicle stimulating hormone (FSH)

4. Luteinizing hormone (LH)

5. Prolactin (PRL)

6. Growth hormone (GH), somatotropin

Three different glycoprotein hormones (___, ___, and ___) are made within the pituitary. These hormones contain one or more N-linked ___ within their structure

TSH, FSH, LH, oligosaccharides

A related peptide, ___ ___ ___, is made by the placenta of pregnant females. During pregnancy, ___ regulates estrogen and progesterone synthesis and secretion by the corpus luteum and placenta.

Each of the glycoprotein hormones is composed of α and ß chains that are non-covalently linked by ___ bonds. The ___ subunits of all glycoprotein hormones are identical (92 amino acids in humans) whereas the ___ subunit of each hormone is structurally distinct. Hormone specificity is conferred by the ___ subunit.

human chorionic gonadotropin (hCG),hCG

disulfide, α, ß, ß

CONTROL OF HORMONAL SECRETION FROM THE PITUITARY

The regulators of anterior pituitary hormone secretion are called ___ hormones (RH).

Releasing hormones are synthesized in ___ cells located in the ___ (most of these hormones are also synthesized in other tissues). Axons of these neurons terminate on ___ located at the base of the hypothalmus (median eminence). The capillary networks give rise to the principal blood supply to the ___ lobe.

Hypothalamic neurosecretory cells secrete releasing hormones into the ___ portal system. The portal system delivers the releasing hormones directly to the ___ pituitary without passing through the ___ circulation.

releasing

neuroendocrine, hypothalamus, capillaries, anterior

hypophyseal, anterior, systemic

Major hypothalamic releasing hormones:

1. Thyrotropin releasing hormone (TRH)-acts on ___ and ___, effect is ___

2. Growth hormone releasing hormone (GHRH)-acts on ___, effect is ___

3. Somatostatin (SRIF or SS)-acts on ___ and ___, effect is ___

4. Gonadotropin releasing hormone (GnRH)-acts on ___, effect is ___

5. Corticotropin releasing hormone (CRH)-acts on ___, effect is ___

6. Dopamine (DA)-acts on ___, effect is ___

1. thyrotrophs, lactotrophs, stimulatory

2. somatotrophs, stimulatory

3. somatotrophs, thyrotrophs, inhibitory

4. gonadotrophs, stimulatory

5. corticotrophs, stiumalotry

6. lactotrophs, inhibitory

Positive feedback occurs when increasing concentrations of one hormone causes a second gland to release a second hormone, which further ___ the output of the first hormone.

Negative feedback occurs when increasing concentrations of one hormone causes the release of a second hormone. The second hormone then ___ the secretion of the first hormone.

Negative feedback is the major physiological ___ mechanism for secretion.

stimulates

inhibits

regulatory

Growth Hormone (___):

Essential for normal growth during ___ and ___.

Circulates in a complex with a ___ protein called ___.

Stimulates the expression of ___ growth factor 1 (IGF-1) in many different tissues.

Growth hormone is released from the ___ in ___.

Somatotropin

childhood, adolescence

binding, GHBP

insulin-like

somatotrophs, pulses

IGF-1 (___):

a potent ___ and ___ factor.

a peptide hormone with sequence homology to ___

The ___ is the major source of circulating IGF-1.

IGF-1 has local ___ effects in many tissues.

IGF-1 binds to a variety of ___ proteins.

Somatomedin

mitogen, differentiation

insulin

liver

paracrine

binding

GH has both ___ and ___ effects:

Its acute effects (mostly metabolic) are ___.


Its longer term effects (mostly on somatic growth) are ___ and mediated through IGF-1.

direct, indirect

direct

indirect

GH hormone acts ___ on liver and peripheral tissues.

Its skeletal effect via IGF-1 is increased ___

Its extraskeletal effect is increased ___ synthesis and cell ___

These are growth ___ effects

indirectly

chondrogenesis, protein, proliferation

promoting

GH acts ___ on fat to increase lipolysis

GH acts ___ on carbohydrates to increase blood glucose

These are metabolic effects

directly

directly

Growth hormone excess:

___ results from excessive secretion of growth hormone in adults, usually the result of benign pituitary ___.

___ is the result of excessive growth hormone secretion that begins in young children or adolescents. It is a very rare disorder, usually resulting from a pituitary ___.

Acromegaly, tumors

Giantism, tumor

Growth Hormone Deficiency:

If untreated, GH deficiency in children results in ___

dwarfism

Because GH is a peptide hormone:

It is broken down into ___ ___ in the gut.

GH replacement therapy is administered by ___.

GH ___ sprays are being tested for effectiveness.

amino acids

injection

nasal

GH levels ___ in adulthood.

decline

In the late 1980's, one study of ~25 subjects reported dramatic effects of Growth Hormone replacement on older adults:

___ lean body mass

___ fat mass

___ vitality

___ physical mobility

___ social behavior

Increased

Decreased

Enhanced

Improved

Improved

Concerns about GH replacement in adults:

IGF-1 is a potent ___. GH therapy could stimulate the growth of ___.

Recent studies suggest that the major long-term benefit in adults is in body mass ___ (muscle versus fat) - other reported benefits are in question.

mitogen, tumors

distribution

Other clinical uses of growth hormone:

___ syndrome: treatment of growth deficit and poor muscle tone.

___ ___ syndrome: promote adaptation of remaining bowel.

___: treatment of muscle wasting.

Prader-Willi

Short bowel

AIDS

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