BBT417

Prepared by Ishrat Jabeen (PhD)

Lecture 03

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Respect your parents, respect your
teachers

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 Mechanisms of Receptor Regulation

• Endocytosis and temporary sequestration in endosomes

• Destruction of the receptors in lysosomes (down-regulation)
• Rapid inactivation by receptor phosphorylation
• A change in a protein involved in signal transduction
• The production of an inhibitor
• Effects of other hormone

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 Steroid and Thyroid Hormone Receptor Resistance
Syndromes
• Receptor inactivity→
• Hormone defficiency
• elevated levels of the circulating hormone ligand
• increased (or inappropriately detectable) levels of the relevant trophic
regulatory hormone (eg, ACTH, TSH, FSH, or LH)
• Androgen receptor mutation
• X-linked
• Thyroid receptor mutation
• β form of the receptor

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 Receptors Upregulation
• Increase in the number of receptors for
the particular hormone
 prevailing levels of the hormone have
been low for some time
• A hormone can also up-regulate the
receptors for another hormone
 Thyroid hormone up-regulates cardiac
adrenergic receptors

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 Control of Hormone Release
• Constitutive (basal) and stimulated (peak
levels).
• The periodic and pulsatile release of hormones
• Plasma levels of hormones Oscillate
throughout the day, showing hormone specific
peaks and troughs.
• Regulated by interaction and integration of
multiple control mechanisms
• hormonal, neural, nutritional, and
environmental factors

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 Control of Hormone
Release

• Hormones can be classified by

their reflex pathways
• Many Endocrine Reflexes
Involve the Nervous System

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 Neural Control

• Direct neurotransmitter control of

endocrine hormone release
• Dopaminergic control of pituitary
prolactin release
• Pancreas receive sympathetic and
parasympathetic input
• Sympathetic regulation of the
adrenal gland

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 Hormonal Control

• Hormone release from an endocrine organ is frequently

controlled by another hormone
• Stimulation and
• Suppression of hormone release
 Negative feedback regulation
 Positive feedback regulation
 Product regulation
Nutrient or Ion Regulation
• Plasma levels of nutrients or ions can also regulate hormone
release
• Insulin release by plasma glucose levels
• control of parathyroid hormone release by plasma
calcium levels.

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Environmental Factors
• Lifestyle factors-showing the clearest association with TSH and thyroid
hormones were smoking, body mass index (BMI) and iodine.
• Smoking mainly led to a decrease in TSH levels and an increase in
triiodothyronine (T3) and thyroxine (T4) levels, while BMI levels were
positively correlated with TSH and free T3 levels.
• Excess iodine led to an increase in TSH levels and a decrease in thyroid
hormone levels.
• Among the pollutants analyzed, a decrease in thyroid hormone levels after
exposure to perchlorate was observed by most studies. 

 doi: 10.3390/ijms22126521

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 Feedback control mechanism
• Release of one hormone can be influenced by more than one of these
mechanisms (neuronal, hormonal, Nutrient)
• The neuroendocrine system adapts to a changing environment to maintain
homeostasis
• The responsiveness of target cells to hormonal action leading to regulation of
hormone release constitutes a feedback control mechanism.
Negative feedback & Positive Feedback
• adaptive changes do not lead to pathologic conditions
• short- and long-term adaptations to changes in the environment

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Levels of feedback mechanisms

Fine tuning of Hormonal activity

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 Assessment of Endocrine Function
• Disorders of the endocrine system result from
alterations in hormone secretion or target cell
responsiveness to hormone action
• Decreased responsiveness
• a decreased number of hormone receptors,
• a decreased concentration of enzyme activated by the
hormone,
• an increased concentration of noncompetitive inhibitor,
• or a decreased number of target cells
• Hormone sensitivity
• Higher hormone concentrations to produce 50% of the
maximal response
• decreased hormone-receptor affinity, number
• increased rate of hormone degradation
• increased levels of antagonistic or competitive
hormones.

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Hormone Measurements RIA

https://www.youtube.com/watch?v=Cs1LvCyEGKg

Cross-reactivity Prohormone
Degradation

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 Limitations of RIA

• Lack of Specificity
• cross-reactivity of the antibody with more than one hormone
• Hormone sharing homology can lead to nonspecific recognition by the
antibody
• Heterogeneous form of hormone in the plasma
• Prohormone, enzymatic degradation
• Presence of circulating endogenous antibodies

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 Hormone Measurements Immunometric Assay

• The binding of the hormone by a

MONOCLONAL ANTIBODY followed by
binding by a SECOND MONOCLONAL
ANTIBODY
to a DIFFERENT ANTIGENIC SITE in the
hormone.
• The concentrations of the antibodies used
can be increased dramatically, speeding
the reaction time and completion of the
assay.

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 Interpretation of Hormone Measurements

• Plasma hormone measurements reflect endocrine function only when

interpreted in the right context
• An abnormality in endocrine function is identified through measurements of
hormone levels, hormone-nutrient or hormone-tropic hormone pairs, or by
functional tests of hormone status.
• The circulating levels of a particular hormone reflect the immediate state of the
individual.

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 Interpretation of Hormone Measurements

Pituitary Target hormone level

hormone
Low Normal High
level

High Primary failure of   Autonomous secretion of pituitary hormone or

target endocrine organ resistance to target hormone action
Normal   Normal  
range
Low Pituitary failure   Autonomous secretion by target endocrine
organ

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