Endocrine system

• Regulatory systems: endocrine vs nervous• Components of the endocrine system• Nature of hormones• Function of hormones• Synthesis, release and regulation of hormones• Transportation and removal of hormones• Pathologies associated with hormones

– In the beginning, we know there are endocrine system from pathologies associated

Nervous regulation is by specific pathways using specialized high-speed conduction routes (nerves). Therefore effects are usually fast with narrow, specific focus.

- Like putting hand on hotplate, very fast responseEndocrine regulation is usually via a non-specific pathway, bloodstream, often with a range of targets. Therefore in most cases effects are usually slow.

- Long term changes ~ minutes, hours, days- Like spam – where most of the body doesn’t

respond to the spam. Only particular individuals would respond

Endocrine system• Regulatory systems: endocrine vs nervous• Components of the endocrine system• Nature of hormones• Function of hormones• Synthesis, release and regulation of hormones• Transportation and removal of hormones• Pathologies associated with hormones

Endocrine system

• Regulatory systems: endocrine vs nervous• Components of the endocrine system• Nature of hormones• Function of hormones• Synthesis, release and regulation of hormones• Transportation and removal of hormones• Pathologies associated with hormones

Types of hormone

Tyrosine derived

Peptide/protein

Cholesterol based

Endocrine system

• Regulatory systems: endocrine vs nervous• Components of the endocrine system• Nature of hormones• Function of hormones• Synthesis, release and regulation of hormones• Transportation and removal of hormones• Pathologies associated with hormones

Four major functions:

• Maintaining internal environment

• Maintaining energy balance

• Growth and development

• Reproduction

Maintaining internal environment

• Fluid balance/electrolytes/volume/blood pressure e.g. ADH, aldosterone, ANF.

• Plasma calcium/phosphate e.g. PTH, calcitonin, vitamin D.

• Bone repair and mineralization e.g. PTH, GH, insulin, sex steroids, cortisol.

Maintaining energy balance

• Utilization of available fuels

• Storage of surplus fuel

• Mobilization of fuel stores

e.g. insulin, epinephrine, glucagon, thyroid hormone.

Growth and development

• Timing and progressions of developmental changes

• Extent of growth and development of organs and overall body size.

e.g. GH, IGF, sex steroids, insulin, thyroid hormones.

Reproduction• Growth, development and maintenance of

reproductive organs• Growth and development of gametes• Patterns of sexual behaviour• Phenotypic sexual differences• Ovulation, spermatogenesis, fertilization,

pregnancy, birth and lactation.

e.g. GNRH, FSH, LH, estrogen, testosterone, inhibin, progesterone.

Endocrine system

• Regulatory systems: endocrine vs nervous• Components of the endocrine system• Nature of hormones• Function of hormones• Synthesis, release and regulation of hormones• Transportation and removal of hormones• Pathologies associated with hormones

Synthesis• Protein and peptide hormones often made as pre or

pro hormones, for secretion and storage, and subsequently proteolytically cleaved to produce the final active hormone.e.g. insulin is synthesized as proinsulin, ACTH is cleaved from pro-opiomelanocortin.

• Epinephrine and norepinephrine and thyroid hormones derive from tyrosine. Epi and norepi derive directly from enzymic modifications of free tyrosine, whereas the tyrosines for thyroid hormones are iodinated and coupled as parts of a large proteinwhich is subsequently proteolyzed in the thyroid gland.

• Steroids all derive from cholesterol which is often taken up in LDLs from the blood by the relevant endocrine glands. E.g. adrenal glands, gonads. Cholesterol enters the mitochondria and is converted by a series of enzymic reactions to the end hormone. The specific end hormone produced depends on the enzymes present in the relevant gland.

e.g. cortisol, aldosterone, estrogen, progesterone, testosterone.

Release

• Protein and peptide hormone are all stored in secretory granules until a relevant signal causes their exocytosis

• Amine hormones (E and NE) are also stored in secretory granules.

• Thyroid hormones and steroid hormones are not retained after synthesis and leave the cell directly.

Regulation

The circulating levels of most hormones are controlled by feedback loops. These are usually negative feedback loops where the rises in the concentration of an end hormone will result in decreases in earlier components of the control process. More complex control loops also occur.

e.g. elevated levels of cortisol shut down ACTH production, rises in testosterone levels decrease LH production.

Endocrine system

• Regulatory systems: endocrine vs nervous• Components of the endocrine system• Nature of hormones• Function of hormones• Synthesis, release and regulation of hormones• Transportation and removal of hormones• Pathologies associated with hormones

Transportation

• Many peptide, protein and amine (E and NE) hormones are largely free in the plasma

• Thyroid and steroid hormones are mostly bound by carrier proteins e.g. thyroxine binding globulin, transcortin, sex steroid binding globulin. Being bound to carrier proteins greatly extends their lifetime in the circulation.

Removal

• Most active hormones are removed by the liver and kidney.

• They are often proteolysed or enzymically modified. Breakdown products of protein and peptides can be recycled, whereas much of the metabolites of other hormones enter the urine or bile.

Endocrine system

• Regulatory systems: endocrine vs nervous• Components of the endocrine system• Nature of hormones• Function of hormones• Synthesis, release and regulation of hormones• Transportation and removal of hormones• Pathologies associated with hormones

Pathologies associated with hormones

Pathologies arise from excess (hypersecretion) or insufficiency (hyposecretion) of a hormone (or inappropriate hormone levels for the prevailing conditions).Both of these conditions can arise as the result of primary or secondary disease.Primary disease arises from problems in the gland producing the end hormone. Secondary disease arises from causes outside the gland which lead to changes in the activity of the otherwise normal gland.

Clinical perspective

Historically much of what we knowabout Endocrinology has been based on an understanding of disease states resulting from over-production or under-production of hormones, or from receptor/post-receptor defects.