Overview of Endocrine Physiology


Download Printable Notes: Click Here
(Wait 5 seconds and then click ‘Skip Ad’ at the top right corner)

Resources – Ganong’s 25th Ed.; Origin of Pictures used is presented underneath.

glandotropic hormones = effect over other hormone-secreting glands; e.g. hypothalamus
aglandotropic hormones = direct effect over target tissues

The endocrine system is defined as:

A distributed system of glands and circulatory messengers, a system often stimulated by the CNS, ANS, or both.

Hormonal Control and Regulation brings about homeostasis at different levels, and over a longer period of time compared to the way the N.S. acts. This is mostly based on a type of feedback from the target tissues: negative feedback.

The messengers of the Endocrine system are termed as hormones, and are of three types:

  1. A.A. derivatives – Hydrophilic
  2. Peptide hormones – Hydrophilic
  3. Steroid hormones – Hydrophobic

Action and reach of hormones:

  • Endocrine – Bloodborne
  • Paracrine – Acts through the Intercellular fluid (ECM)
  • Autocrine – Hormone-secreting cells stimulate themselves/or inhibit.
  • Neurocrine – E.g. the release of hormones from neuronal endings (e.g. Herring bodies in the pituitary)

A hierarchy is established to understand the relation between endocrine glands to target tissues:

  1. Hypothalamus – Controls most of the endocrine system
  2. Pituitary gland – Controlled by the hypothalamus, in turn controls other glands and tissues
  3. Glands and tissues – They respond to stimuli by negative feedback or positive feedback.

Synthesis and Processing of Hormones

  • Multiple hormones may be derived from the same initial precursor. This provides somewhat a ‘genetic economy.
  • All precursors are inactive. This is regarded as a regulatory mechanism.

steroid-hormone-synthesis

Peptides – Regulate at the level of gene transcription
Amines and Steroids – Regulate at the level of enzyme synthesis and substrate availability

In some cases, hormone synthesis may be regulated via effects on translation (e.g. high blood glucose results in a higher rate of translation of insulin mRNA).

Secretion

  • Many hormones are secreted by the exocytosis of stored granules, when the cells are stimulated by a specific signal, e.g. neurotransmitter/peptide releasing factor.
  • Other hormones are continually released by diffusion. The rate at which this happens is influenced by the kinetics of synthetic enzymes or carrier proteins.
  • Some hormones are released in a pulsatile manner, i.e. at intervals of hours, days or months. The intervals are dictated by oscillators in the hypothalamus.
    • Those oscillators regulate the membrane potential of neurons, which secrete hormone releasing factors in the hypophyseal blood flow. These, in turn, cause the release of pituitary & other downstream hormones in a pulsatile manner.178_pituitary_gland_enTaken from http://m.harunyahya.com/tr/Buku/9599/The-Human-Miracle/chapter/4923/Splendid-communication-within-the-body-The-hormone-system
  • Hormone secretion may be regulated by other hormones via negative feedback. For instance, TRH is inhibited by Thyroid hormones.

Hormone Transport in Blood

In addition to rate of secretion (steady vs. pulsatile) and the nature of a hormone, there are a number of other factors that influence the circulating levels of hormones:

  1. Affinity of a hormone to their plasma carriers
  2. Rate of degradation & Rate of reuptake
  3. Receptor binding & avability of receptors

The stability of a hormone influences its half-life(λ), and this has therapeutic implications for hormone replacement therapy.

Plasma carriers

  • Serve as a reserve for inactive hormones
  • Prevents uptake/degradation
  • Restrict the access of some hormones to the target site

Catecholamines & most peptide hormones are soluble in plasma, and transported as such.
In contrast, steroid hormones are transported bound to large proteins – steroid binding proteins (SBP), which are synthesised in the liver.

E.g. Sex-hormone binding globulin (SHBG) is a glycoprotein that transports testosterone and 17β-Estradiol.
Progesterone and Cortisol are transported bound to transcortin.

SBP-hormone complex is in equilibrium with free hormones in the blood.

SBP-hormone complex ↔ Free hormone

Only the free hormone can diffuse across cell membranes!

SBPs have three main functions:

  1. Increase solubility of the lipid-based hormones
  2. Reduce rate of loss of hormone by preventing them from being filtered out
  3. Provide a source of hormone that can release free hormone as the equilibrium changes

Hormone Action

  • Exert a wide range of distinctive actions on a large number of target
  • Effect changes in metabolism
  • Affect the release of other hormones and regulatory substances
  • Change the activity of ion channels
  • Affect cell growth

Hydrophilic hormones act on receptors on the cell membrane – mostly GPCRs – , while the sterol hormones act on intracellular nuclear receptors.

Steroid & Thryoid hormones are distinguished by their predominantly intracellular site of action, since they can diffuse through the cellular membrane.

  • They bind cytoplasmic proteins known as nuclear receptors
  • Upon binding, they receptor-ligand complex translocates in the nucleus where
  • It homodimerises or heterodimerises (associates with a distinct liganded nuclear receptor).
  • The dimer binds to the DNA to either increase or decrease gene transcription of a particular target sequence.

extranuclear receptors for steroids = mediate fast responses (e.g. plasma membrane receptors for oestrogen can mediate acute arterial vasodilation as well as reducing cardiac hypertrophy in a pathophysiologic setting. Such functions may account for the difference in the prevalence of cardiovascular disease in premenopausual and postmenopausal women).

Feedback – e.g. Homeostasis of blood osmolality

slide_84Picture taken from http://slideplayer.com/slide/273330/

Disorders of the Endocrine System

  1. Hormone Deficiencies – E.g. Type I Diabetes Mellitus, lacking insulin.
    • Are most commonly seen in the setting where the gland has been destroyed, for instance by an autoimmune disorder.
    • Inherited mutations have lead to deficiencies of hormones or receptors for the hormones
    • May also result from a lack of appropriate precursors of hormones
  2. Resistance to Hormones – E.g. Type II Diabetes Mellitus, resistance to insulin.
    • Adequate levels of hormone are synthesised and released, but the target tissues are resistant to the hormones’ effects (Receptor doesn’t bind the hormone)
    • Resistance may result from inherited mutations at the level of hormone receptors, or it may be developed.
  3. Excess of Hormone – E.g. Gigantism
    • Usually results from an endocrine tumour which may produce a hormone in an excessive and uncontrolled matter.
      A tumour may not only mimic one gland, but multiple, and thus producing multiple types of hormones.
    • The secretion of the tumour hormones may not be subject to the same types of feedback regulation seen for the normal source of that hormone
    • When hormone production is  increased there usually will also be a downregulation of upstream releasing factors due to triggering of negative feedback loops.
    • Disorders of hormone excess can also be mimicked by antibodies that bind to, and activate the receptor for a hormone.

CLINICAL

Graves’ Disease – Susceptible individuals generate thyroid-stimulating immunoglobulins

Breast Cancer 

  • Most common malignancy in women, 1 million per year
  • Proliferation of 2/3 of tumours are driven by oestrogens
    • Cancerous cells express high levels of posttranslationally  modified oestrogen receptors.
    • It was reported by Sir Thomas Beatson that disease progression was delayed in women following an ovaries removal procedure.
  • ER+ tumours = Dependent on ovary-secreted oestrogens
  • ER- tumours = Dependent on testosterone-originating oestrogens (postmenstrual women).
Advertisements