Endocrine Hormone Structure and Function, Hormone Receptors and Signaling

Introduction to Endocrine Hormones

  • Overview of Class Topics:

    • Discussion of endocrine hormones, covering structure, function, and mechanisms of hormone action.

    • Emphasis on the importance of hormones in physiological processes, stating that all bodily functions rely on hormones.

    • Continuous activity of cells in the body, even during sleep, underscores the importance of understanding hormones in physiology.

Importance of Endocrine Hormones

  • Role in Physiology:

    • Constitute a foundation for all physiology lectures.

    • All physiological functions depend on hormonal mechanisms (e.g. cognition, movement).

  • Clinical Implications:

    • Hormone receptor defects may arise from genetic mechanisms such as mutations or polymorphisms.

    • These defects can cause various disease processes.

Learning Objectives for the Lecture

  • Objectives:

    • Describe the structure-function relationship of various endocrine hormones.

    • Explain feedback regulation concepts regarding hormone production.

    • Recognize the importance of plasma binding proteins in circulating inactive hormones.

    • Understand peptide hormone secretion mechanisms.

    • Recognize hormone-receptor specificity and the process of downregulation.

    • Differentiate among hormone responsiveness and hormone sensitivity.

    • Describe assay systems for hormone concentration in plasma and urine samples.

    • Compare and contrast natriuretic peptide hormone and cyclic GMP signaling mechanisms.

Homeostasis and Hormonal Action

  • Definition of Hormones:

    • Chemical substances produced by specific cells, released into the bloodstream, and carried to target cells to exert actions.

    • Hormones can also act within neighboring cells or locally (paracrine and autocrine signaling).

  • Feedback Regulation:

    • Positive and negative feedback mechanisms maintain hormonal regulation to achieve homeostasis.

    • Disruptions to homeostasis can lead to disease.

  • Homeostasis Definition:

    • Derived from Greek words "homeios" (similar) and "status" (standby).

    • Homeostasis is easier to maintain in youth but becomes more difficult with age and environmental change.

Classification of Hormones

  • Types of Hormones:

    • Endocrine Hormones: Produced by one cell, carried by the bloodstream to distant cells.

    • Neurotransmitters: Similar in function to endocrine hormones, produced by neurons.

    • Paracrine Hormones: Affect neighboring cells (e.g. endothelial hormones affecting smooth muscle).

    • Autocrine Hormones: Act on the same cell that produced them.

Hormonal Receptor Mechanism

  • Hormonal Binding Processes:

    • Hormones bind to specific membrane receptors (N-terminal outside the cell).

    • Hormone-receptor binding initiates intracellular signaling, involving gene transcription and translation leading to biological responses.

  • Second Messengers:

    • Hormones act as first messengers; second messengers (e.g. cAMP, cGMP, calcium) carry the hormonal signal within the cell.

  • Known Second Messengers:

    • Only five major second messengers have been discovered:

    • cAMP

    • cGMP

    • Calcium

    • Inositol trisphosphate

    • Diacylglycerol

Hormone Turnover and Measurement

  • Metabolic Clearance Rate (MCR):

    • Defined as the volume of plasma cleared of the hormone per minute.

    • MCR can be calculated using:

    • MCR=milligram per minute removedmilligram per milliliter in plasmaMCR = \frac{\text{milligram per minute removed}}{\text{milligram per milliliter in plasma}}

  • Degradation Targets:

    • Liver and kidney are primary sites of hormone degradation.

    • Various biochemical processes are involved in hormone degradation.

  • Assay Systems:

    • Hormones can be measured in plasma and urine using:

    • Radioimmunoassay (RIA)

    • Enzyme-linked immunosorbent assay (ELISA)

Feedback Mechanisms in Hormone Regulation

  • Negative Feedback Mechanism:

    • Conditions such as high circulating hormone levels inhibit further hormone production.

    • Hormones can also activate or deactivate feedback loops within the hypothalamic-pituitary axis to regulate secretion of other hormones.

  • Positive Feedback Mechanism:

    • Less common in hormonal regulation; typically promotes process continuation rather than cessation.

Hormonal Types - A Brief Overview

  • Major Endocrine Glands and their Hormones:

    • Anterior Pituitary:

    • Adrenocorticotropic hormone (ACTH), Growth hormone (GH), Prolactin (PRL), Thyroid-stimulating hormone (TSH), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH).

    • Posterior Pituitary:

    • Antidiuretic hormone (ADH), Oxytocin.

    • Thyroid Gland:

    • Thyroxine (T4), Triiodothyronine (T3).

    • Parathyroid:

    • Parathyroid hormone (PTH).

    • Hormones from Gonads:

    • Testosterone (Testes), Estradiol (Ovaries).

    • Pancreas:

    • Insulin, Glucagon.

Hormone Synthesis, Storage, and Secretion

  • Peptide Hormones:

    • Produced from the gene action; initial form is preprohormone, which is cleaved to prohormone before being modified in the Golgi apparatus.

    • Stored in secretory granules, released upon cellular stimulation via exocytosis.

  • Steroid Hormones:

    • Derived from cholesterol, not stored in granules—released immediately after synthesis.

Specific Hormonal Actions

  • Calcium and cAMP in Hormone Secretion:

    • Calcium and cyclic AMP are crucial in facilitating the movement of hormone-containing granules towards the plasma membrane for release.

Conclusion

  • Hormones regulate various physiological mechanisms and processes necessary for maintaining homeostasis throughout an individual's life cycle.