PLASMA CONCENTRATION OF HORMONE ENDO BLOCK 412 LECTURE

PLASMA CONCENTRATION OF HORMONE ENDO BLOCK 412 LECTURE - 2 Dr. Shaikh Mujeeb Ahmed Assistant Professor Al. Maarefa College

Objectives • Explaining the factors influencing the plasma concentrations of hormones • Recognizing the different types of hormone interactions and the significance of hormone concentrations • Explain the principles of positive and negative feedback control of hormone secretion. • Explain the effects of secretion, excretion, degradation, and volume of distribution on the concentration of a hormone in blood plasma. • List hormone measurements assays. • Identifying the most common causes of endocrine dysfunctions.

The effective plasma conc. of a hormone • Depends on; – The hormone’s rate of secretion into the blood by the endocrine gland. – Its rate of metabolic activation or conversion. eg. T 4 to T 3 or conversion of small amount of testosterone to estrogen – For lipophilic hormones, its extent of binding to plasma proteins. eg. during pregnancy the level of thyroid hormone is high even with normal thyroid function. – Its rate of removal from the blood by metabolic inactivation and excretion in the urine.

Cont…. • The effective plasma concentration of a hormone is normally regulated by changes in the rate of its secretion.

Control of Hormone Secretion 1. Diurnal Rhythm • Day–night Example increase Prolactin secretion during night. 2. Circadian Rhythm • circadian (“around a day”) rhythm, which is characterized by repetitive oscillations in hormone levels that are very regular and cycle once every 24 hours. Example Cortisol 3. Sleep Wake Rhythm • Example Infants / Children increase GH during sleep increase ACTH and Cortisol during sleep 5

Control of Hormone Secretion 4. Infradian Rhythm • Ovarian steroids – Estrogen & Progesterone 5. Developmental Rhythm • Example Growth Rhythm 6. Ultradian Rhythm • moment to moment change Example insulin 6

The effective plasma conc. of a hormone is regulated by • Negative Feedback control. – Negative feedback exists when the output of a system counteracts a change in input, maintaining a controlled variable within a narrow range around a set level

The effective plasma conc. of a hormone is regulated by • DIURNAL (CIRCADIAN) RHYTHMS – The most common endocrine rhythm is the diurnal (“day–night”), or circadian (“around a day”) rhythm, which is characterized by repetitive oscillations in hormone levels that are very regular and cycle once every 24 hours.

CIRCADIAN (“AROUND A DAY”) RHYTHM

NEUROENDOCRINE REFLEX • Sudden increase in hormone secretion in response to a specific stimulus.

Endocrine disorders Result mainly from 1. Hormone excess (hyper secretion)or 2. Deficiency (hypo secretion)or 3. Decreased target-cell responsiveness

HYPOSECRETION • Primary hyposecretion occurs when an endocrine gland is secreting too little of its hormone because of an abnormality within that gland • Secondary hyposecretion takes place when an endocrine gland is normal but is secreting too little hormone because of a deficiency of its tropic hormone.

HYPOSECRETION • Primary hyposecretion • genetic (inborn absence of an enzyme that catalyzes synthesis of the hormone, such as the inability to synthesize cortisol because of the lack of a specific enzyme in the adrenal cortex

HYPOSECRETION • Dietary (lack of iodine, which is needed for synthesis of thyroid hormone); • Chemical or toxic (certain insecticide residues may destroy the adrenal cortex); • Immunologic (autoimmune antibodies may destroy the body’s own thyroid tissue); • Other disease processes (cancer or tuberculosis may coincidentally destroy endocrine glands); • Iatrogenic (physician induced, such as surgical removal of a cancerous thyroid gland); and • Idiopathic (meaning the cause is not known).

Hyper secretion • Primary hyper secretion – When the defect lies within the gland itself • Secondary hyper secretion – Results from excessive stimulation from the outside • Tumor • Immunological defect - excessive stimulation of the thyroid gland by an abnormal antibody that mimics the action of TSH, the thyroid tropic hormone. • Substance abuse - athletes of using certain steroids that increase muscle mass by promoting protein synthesis in muscle cells

Target-cell (receptor)responsiveness • Down regulation of receptors • Its an important locally acting negativefeedback mechanism that prevents the target cells from overreacting to a prolonged high concentration of insulin; that is, the target cells are desensitized to insulin, helping blunt the effect of insulin hypersecretion.

Target-cell (receptor)responsiveness • Up Regulation regulation of receptors • A mechanism in which a hormone increases the number or affinity of its receptors. Upregulation may occur by increasing synthesis of new receptors, decreasing degradation of existing receptors, or activating receptors

PERMISSIVENESS, SYNERGISM, AND ANTAGONISM • Permissiveness, – one hormone must be present in adequate amounts for the full exertion of another hormone’s effect. thyroid hormone increases the number of receptors for epinephrine in epinephrine’s target cells. • Synergism – occurs when the actions of several hormones are complementary and their combined effect is greater than the sum of their separate effects – Presence of FSH & Testosterone for effective spermatogenesis.

Cont. . • Antagonism – occurs when one hormone causes the loss of another hormone’s receptors, reducing the effectiveness of the second hormone – Progesterone (a hormone secreted during pregnancy that decreases contractions of the uterus) inhibits uterine responsiveness to estrogen.

Table 18 -1, p. 665

Hormone conc. measurement • Hormone conc. can be measured by highly specific and sensitive radioimmunoassay. • Serum sample with unknown conc. of hormone is mixed with known amount of antibodies to that hormone plus radioactively labeled hormone. • Both hormone & the radio labeled hormone compete for the antibodies.

Hormone conc. measurement • Higher the conc. of unlabeled hormone in the sample, the less radio labeled hormone could bind with Ab. So more radiolabeled free hormone in solution. • A standard curve is prepared

References • Human physiology, Lauralee Sherwood, seventh edition. • Text book physiology by Guyton &Hall, 11 th edition. • Physiology by Berne and Levy, sixth edition.