The Endocrine System: Functions and Mechanisms

• The hypothalamus controls the pituitary gland, which secretes various hormones affecting other glands.

The Endocrine System's Functions

• Development, including proliferation, growth, differentiation, and organogenesis.
• Reproduction, including sexual maturation, behavior, maintenance of pregnancy, and lactation.
• Metabolism, which involves carbohydrate and energy storage, metabolic rate, and temperature regulation.
• Homeostasis, including water balance as well as salt levels, blood volume, and pressure.

How the Endocrine System Works

• Hormones act as messenger molecules in the endocrine system.
• The hormones can alter the structure and activity of target cells through specific hormone receptors.
• This includes stimulating DNA synthesis and the transcription or translation of mRNAs.
• Channel proteins and enzymes are affected by modifying their shape.
• The endocrine system helps maintain a constant internal environment (homeostasis).
• Changes or disorders involving endocrine tissues leads to physiological consequences.

Hypothalamus and Posterior Pituitary

• The hypothalamus is an area at the base of the brain.
• Neurons send axons from the hypothalamus to the posterior pituitary.
• The posterior pituitary is a neuroendocrine organ that releases oxytocin and vasopressin (ADH).
• Oxytocin and ADH enter the venous drainage to reach target tissues.
• The posterior pituitary has a neuronal developmental origin as a down-growth from the diencephalon.

Oxytocin

• Parturition involves uterus contraction to expel fetus.
• Altered estrogen/progesterone balance leads to increased excitability of the uterus.
• Uterine contractions occur as the fetus presses on the cervix, signalling the hypothalamus.
• Oxytocin secretion results, leading to further uterine contractions.
• Birth terminates the positive feedback loop.
• Oxytocin is also involved in milk ejection reflex during breastfeeding, and maternal behavior.
• Group bonding, empathy and autism are possibly linked to oxytocin.

Pituitary Anatomy

• The anterior pituitary originates from ectoderm.
• Neurons in the hypothalamus send axons to the median eminence.
• Neuropeptide hormones released at the median eminence enter the portal vessels.
• These hormones control the release of hormones from the anterior pituitary.
• Hormones released from the anterior pituitary enter the venous drainage to reach their target tissues.
• The anterior pituitary secretes growth hormone (GH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and prolactin (PL).

Histology of the Anterior Pituitary

• Haemotoxylin and Eosin stains show chromophobes, acidophils, basophils and capillaries of the anterior pituitary.

Main Pituitary Hormones

• The posterior pituitary is neuronal.
• The posterior pituitary releases oxytocin and vasopressin (antidiuretic hormone/ADH).
• The anterior pituitary is ectodermal, and it secretes GH, FSH, LH, ACTH, TSH, and PL.
• Cells in the hypothalamus release peptide hormones (neurohormones) into the portal blood vessels at the median eminence.
• These hypothalamic hormones influence the release of hormones from the anterior pituitary.

Releasing and Inhibiting Hormones

• Releasing hormones of the hypothalamus include:
  • Growth hormone releasing hormone (GHRH), for growth hormone (GH).
  • Corticotropin releasing hormone (CRH), for corticotropin (ACTH).
  • Thyrotropin-releasing hormone (TRH), for thyroid-stimulating hormone (TSH).
  • Gonadotropin releasing hormone (GnRH), for luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
• Inhibiting hormones of the hypothalamus include:
  • Somatostatin (SS), which inhibits growth hormone (GH) and thyroid-stimulating hormone (TSH).
  • Dopamine (DA), which inhibits prolactin (PRL).

Anterior Pituitary Hormones: FSH/LH

• Luteinizing and follicle-stimulating hormones (FSH/LH) are made in luteotrophs (gonadotrophs).
• FSH/LH are released in response to hypothalamic GnRH.
• FSH/LH control production of steroid hormones.
• In ovaries, FSH/LH control estrogen and progesterone production.
• In testes, FSH/LH control testosterone production.
• Gonadal steroids control sexual differentiation, behavior, and fertility.

Loss of FSH/LH Secretion

• Loss of function in children prevents puberty.
• Calorie restriction in adults (anorexia, excessive exercise) causes loss of reproductive function.
• Administration of GnRH, FSH/LH is used to manipulate reproduction, for example, to induce multiple births as a side-effect of IVF.

Anterior Pituitary Hormones: GH

• Growth hormone (GH) is made in somatotrophs.
• GH is released in response to hypothalamic GHRH and inhibited by hypothalamic SS.
• GH has a direct anabolic effect in many tissues.
• GH targets the liver to produce somatomedins (insulin-like growth factor-1/IGF-1).
• Somatomedins stimulate growth in many tissues.

Lack of GH

• Lack of GH causes short stature, which GH treatment can alleviate.
• Pituitary dwarfism is the failure of growth hormone secretion or action.
• Subjects with pituitary dwarfism have proportionately smaller stature. -Commonest form of dwarfism, achondroplasia, is not caused by growth hormone deficiency but by FGFR mutation leading to abnormal bone growth.

Too Much GH

• Too much GH leads to gigantism if secreted throughout childhood.
• Too much GH leads to acromegaly if secreted after bones have fused.
• Acromegaly leads to continuous growth of hands, feet, and jaws.
• Acromegaly is an over-secretion of GH in adulthood, usually due to a pituitary adenoma.

Anterior Pituitary Hormones: TSH

• Thyroid stimulating hormone (TSH) is made in thyrotrophs and released in response to hypothalamic TRH.
• TSH acts on the thyroid to generate triiodothyronine (T3) and thyroxine (T4).
• T3 and T4 regulate growth and development.
• Not enough thryoid hormones can cause hypothyrodism.
• Toxic Goitre (hyperthyroidism with enlarged thyroid) and exophthalmos (bulging eyes) are the result of too much thyroid hormones.

Anterior Pituitary Hormones: PRL

• Prolactin (PRL) is made in mammotrophs and its release is inhibited by hypothalamic dopamine.
• Prolactin stimulates lactation in the post-partum period.
• Oversecretion of Prolactin leads to loss of reproductive function.
• Gynecomastia in males can be caused by too much prolactin.

Anterior Pituitary Hormones: ACTH

• Adrenocorticotropic hormone (ACTH) is produced and secreted by the anterior pituitary gland (corticotrophs).
• ACTH is released in response to hypothalamic CRH.
• ACTH acts on the cortex of the adrenal gland to produce and release steroid hormones.
• Adrenal steroid hormones regulate sodium balance, blood pressure, metabolism, and responses to stress.
• Too much adrenal steroids leads to Cushings syndrome, and symptoms such as obesity of face and trunk, hirsutism, and skin discolouration.

Disorders of the Endocrine System

• Endocrine disorders may involve excess secretion of a hormone, such as acromegaly or giantism. – Acromegaly and giantism are caused by too much growth hormone. -Too much cortisol causes Cushing’s syndrome.

• Deficient secretion of a hormone leads to type 1 diabetes (no insulin), Addison’s disease, which produces adrenal cortisol deficiency), or thyroid insufficiency.

• Failure to respond to a hormone is another kind of disorder. – This leads to type 2 diabetes, insulin resistance), or growth hormone receptor defects.

Feedback Control of Hormone Secretion

• An external stimulus activates an endocrine cell, which releases a hormone into the blood.
• The hormone is rapidly cleared from the circulation by the liver or kidneys.
• The target tissue responds to the hormone.
• This response reduces the initial stimulus via a negative feedback loop.
• Negative feedback control loops ensures homeostasis.
• GH release from the pituitary is stimulated by GHRH but inhibited by somatostatin (SS).
• GH released from the pituitary feeds back on the hypothalamus to inhibit GHRH.
• Insulin-like growth factor-1 (IGF-1) released from the liver feeds back to inhibit GH release from the pituitary.
• IGF-1 feeds back on the hypothalamus to increase SS release.

Feedback Loops

• TSH produces T3/T4, and T3/T4 negatively affect TSH production.
• Oxytocin release during parturition is an example of positive feedback.
• In long and short feedback loops, Stimulus -> Hypothalamus -> Anterior Pituitary -> Endocrine Gland -> Target Tissue -> Response.
• A successful compensation will result in homeostasis established, while a failure to compensate leads to pathophysiology, illness, and death.