Lecture 2: Environmental Influences on The Endocrine System

Factors Affecting the Endocrine System

• The system responds rapidly to external changes in the environment e.g.

  • Light/ dark e.g. day length

  • Stress – e.g. predators – fight or flight

  • Temperature

  • Food supply

    • Factors have a direct influence

Pituitary Stalk

• Connect the Pituitary Gland to The Hypothalamus

• Anatomical link between the nervous system and endocrine system      

• Central regulatory component of the endocrine system

• The endocrine gland (pituitary) is below the hypothalamus – key part of CNS

  • aka supraoptic-hypothalamic tract

Inputs to Hypothalamus

• Hypothalamus receives information about changes in the environment e.g. cold, stress, puberty, dehydration, exercise, breastfeeding growth etc through neural inputs from other brain areas, including:

  • Limbic system; Brain stem; Reticular formation; Thalamus; Subthalamus; Basal ganglial; Retina; Neocortex (possibly)

• These brain areas sense changes and signal the hypothalamus to integrate the information and produce a response via the pituitary gland.

Pituitary Gland

• Master endocrine gland that takes (electrical) signals from neuronal/ chemical input to elicit a response 

• May influence other glands (indirect) or have a direct impact on physiological processes

• Multiple functions - mediated by trophic effects

• Consist of 2 regions

  • Anterior PG

  • Posterior PG

Anterior and Posterior Pituitary Gland

• 2 distinct regions of the Pituitary

• Respond to, and produce, different hormonal products – ‘separate glands that share blood supply’

  • have no direct functional interaction with each other

Hypothalamus Pituitary Axis

Effect of Low Temperature (Hypothalamus-Pituitary Axis)

• Stimuli detected by hypothalamus

• Hypothalamus releases thyrotropin-releasing hormone (TRH)

• TRH is sent to the anterior pituitary gland to stimulate the secretion of Thyroid-stimulating Hormone (TSH)

• Trophic hormone influences the Thyroid Gland to produce Thyroid hormones

• Results in

  • ↑ metabolism

  • Heat production – body adapts to low temp

Trophic Effect

• One gland i.e. anterior pituitary, has an effect on another endocrine gland which then acts on the body

Non-Trophic Effects

• Anterior pituitary gland has direct action on the body

Posterior Pituitary Gland

• Linked to the hypothalamus by long magnocellular neurons

• Tissue present in mainly neuronal - single nerves that extend into the gland

  • ‘like an extension of the brain’

• Only stores and secretes oxytocin and ADH -

  • Involved in their secretion directly from supraoptic and paraventricular nuclei of the hypothalamus

Magnocellular Neurons

• Cell bodies located in the 3rd ventricle and extend down the pituitary stalk and axons

  • Directly link axons to blood vessels in the PPG

• Contained within the Supraoptic and paraventricular nuclei - Extend down into the gland

  • Releases oxytocin and ADH

Synthesis and Transport of PPG Hormones

• Hormones are produced by cell bodies within the hypothalamus;

• Transported down long axons are stored in nerve endings in storage granules before release

Nuclei

• A collection of neurons with a similar function close together

General Principle of Hypothalamic Control of PPG

• Nerve cell bodies in the hypothalamus produce a hormone packaged into a granule that is transported to the nerve endings and is stored until released into the blood vessel

  • Form of neuroendocrine hormone control with oxytocin and vasopressin (ADH)

Secretion of Oxytocin and Vasopressin From PPG

• Following stimulation hormone is released in blood vessels to be distributed around the body

Dysregulation of ADH or Oxytocin

• Leads to diabetes insipidus or inapproprate secretion

Anterior Pitutiary Gland

• Has many endocrine cell types and different releasing hormones from the hypothalamus will be released into the blood supply and will interact with cells to cause the release of other hormones

  • binds to receptors on specific cells

• Once released, hormones are transported through the body through the main blood supply to target cells

  • has short parvocellular neurons connecting between the hypolathalamus and the gland

Hypothalamic Communication With APG

• Gland communicates with the lateral wall of 3rd ventricle of the Hypothalamus

• Small parvocellular neurons pass to median eminence

• APG receives releasing hormone from the hypothalamus via the median eminence capillary network

• No direct nervous connection can be demonstrated

Median Eminence

• Contains the primary portal system of capillaries;

• Parvocellular neurons linked to this capillary network are located above APG

Parvocellular Neurons

• Receives and integrates signals from other brain regions

• Site of releasing hormone synthesis

  • Release releasing hormones into the capillaries of the median eminence in the primary plexus to influence secretion from APG

• Decides whether to secrete or inhibit the release of releasing hormones and then transmits to APG in response

Hypothalamic Portal Blood System

• Portal capillary system of the human hypothalamus and anterior pituitary.

• Neurohormones are released from the axon termini of the hypothalamic neurons into the primary plexus.

• They are then transported through the vessels to the secondary plexus from which they move through fenestrations in the capillary walls to interact with specific receptors in target cells of APG.

Signal Amplification in Hormone Axis

• Mediated by the production/ release of tropic and non-tropic hormones from APG e.g.

  • e.g. ng level of hormones from hypothalamus required to influence APG

  • peripheral hormone – short half-life- reaches target cells quickly

  • in APG larger levels (ug) are needed to travel and act on the endocrine gland

  • mg levels of hormones released by endocrine gland – travels distance in circulation to target; longer half-life

Feedback Loops

• Essential feature of hormone-gland axis amplification regulation

  • Can be short or long loops

• Peripheral hormones from the endocrine gland will have negative feedback on hormones produced by APG - stop production

Additional Role of Hypothalamic Releasing Hormones e.g. Thyrotropin Releasing Hormone

• Regulates other systems

  • In hypothalamus - TSH release

  • Other brain regions – regulate appetite and mood

Orexins (Orexin A & B)

• Aka hypocretins

• Neuropeptide hormones

• Released from cells in lateral and posterior hypothalamus      

  • Promote wakefulness and eating     

  • Secretion inhibited by glucose and leptin      

  • Narcolepsy

Methods of Clinical and Experimental Demonstrations of Hypothalamic Pituitary Axis

• In-vitro experiments

• Historic in-vivo experiments

• Case studies

Lesion Studies

• Damaging specific areas of the hypothalamus or posterior pituitary can help identify their roles in hormone regulation

Electrophysiology

• Recording electrical activity in the hypothalamus and posterior pituitary reveals neural signals involved in hormone release

Theory for In Vitro Demonstrations of HPA

• Chemical messengers (i.e. “releasing hormones”), synthesised within the hypothalamus, stimulate the release of hormones from the pituitary gland into the general circulation

  • Tested by the measurement of the pituitary response to hypothalamic extracts in an in vitro pituitary system

Testing of In Vitro HPA

• ACTH release from isolated anterior pituitary cells      

• Test tube with isolated APG cells releasing hormones e.g. ACTH 

  • In test tube – receive no input/ stimulus from the environment; overtime amount of ACTH released decreases  

  • Hypothalamic tissue added after day 5 and secretes factors that lead to increased ACTH release 

    • Semi-permeable membrane can be added to show the communication is chemical, not physical

In Vitro HPA: Conclusions

• Hypothalamic cells produce and release a soluble factor that can stimulate the release of ACTH from pituitary cells  

• Shows a chemical communication between hypothalamic and APG cells

Actions of Adrenocorticotropic Hormone (ACTH)

• Released in response to CRH from the hypothalamus acting on APG corticotrope cells

• Causes the release of glucocorticoids from the adrenal cortex

• Negative feedback - cortisol feedbacks to the APG to inhibit corticotropes and ACTH

Blair Bell - Experimental Observations on The Pitutary

• Brain surgery carried out in dogs to physically clamp infundibular stalk, located between the hypothalamus and pituitary,

  • Tied it off and physically prevented communication between the hypothalamus and APG, blocking secretions

Separation of the Infundibular Stalk Between Hypothalamus and Pituitary

• Blood supply from Hyp to PG was therefore reduced or prevented – neural and chemical communication was prevented

• Resulted in

  • Weight gain

  • Dystrophia adiposo-genitals

  •   Genital and mammary atrophy

  • Anterior pituitary atrophy

Consequence of Infindubular Stalk Clamping on PRL, FSH and LH Production

• Hypothalamus will secrete GnRH, stimulating the production of Prolactin, FSH and LH      

• Clamping blocks GnRH communication with APG

• Interrupts FSH and LH production – no GnRH released

  • No inhibition of prolactin – excess secretion, producing morphological effects

Clinical Case Study of 16yr Old Craniopharyngioma Compressing PG and Hypothalamus

• Tumour in bony tissue around PG - Prevent hypothalamus and PG communication

• Resulted in:

  • Obesity      

  • Failure to enter puberty      

  • Small testes      

  • Headaches      

  • Visual abnormalities - tumor compresses optic nerve

  • Froelich’s disease (adiposogenital dystrophy) - secondary to tumour

    • visual disturbances, delayed puberty and breast development

• Treatment via tumour removal

Mediation and Modulation of Actions Between Hypothalamus and Neuonons

• Diverse chemical messengers within the brain mediate inputs between neurons and the hypothalamus, and may also modulate the actions of each other.

• Brain adapts to the environment through neural connections with other neurons in the hypothalamus

• Neurons in the hypothalamus then influence the PG to secrete or inhibit hormones which can go onto to have direct or indirect actions on the body through other endocrine glands

APG Secretions

• Secretes a range of hormones in response to “releasing hormone” signals from the hypothalamus.

• Hormones released:

  • ACTH

  • TSH

  • FSH

  • LH

  • GH

  • PRL