Endocrine System

Proinsulin

• Proinsulin is secreted by the pancreas into the blood.
• It is a key regulator of metabolism and is present in roughly equimolar amounts with insulin in the blood
• Proinsulin has a bioactive effect on microvascular blood flow and tissue health
• Proinsulin has 4 amino acid residues that are removed to form mature insulin.

Steroid Hormone Synthesis

• Steroid hormones are primarily produced in the adrenal cortex, the gonads (testes and ovaries), and the placenta during pregnancy.
• Synthesis of steroid hormones is initiated by G protein-coupled receptor signaling.
• The signal is then transduced through cyclic AMP (cAMP) and protein kinase A (PKA).
• Caffeine and theophylline act as inhibitors of PKA, which is the enzyme involved in signaling and the synthesis of steroid hormones.

Steroid Hormone Circulation

• Steroid hormones circulate in the plasma and reversibly bind to carrier proteins such as albumin.
• Steroid hormones are taken up from the extracellular fluid.
• Also, it is possible that steroid hormones can be synthesized intracellularly.

Steroid Hormones - Adrenal Cortex

• The major hormones produced in the adrenal cortex include:
  • Glucocorticoids, which also have weak mineralocorticoid activity
  • Mineralocorticoids
  • Androgens

Steroid Hormones - Gonads

• Gonads use the same androgen pathway used in the adrenal cortex.
• The gonads produce the following hormones:
  • Estrogens
  • Progestins

Water-Soluble Hormone Signaling

• Water-soluble hormones use second messengers, such as cAMP and calcium ions (Ca2+), to signal in the cells.
• Water-soluble hormones can activate enzymes through receptors such as Janus kinase (JAK)
• Some water-soluble hormone receptors have intrinsic enzymatic activity, such as tyrosine kinase.

Lipid-Soluble Hormone Signaling

• Lipid-soluble hormones are poorly soluble and need carrier proteins in order to move through the plasma.
• These hormones can diffuse through cell membranes.
• They bind to intracellular receptors that act as transcription factors, controlling gene expression.

Hormone Action

• Hormones are transported throughout the body in the blood.
• They can reach all tissues, BUT the response to the hormone is cell-type specific.
• Continuous exposure to low concentrations of a hormone can cause upregulation of cell receptors, making the cells more sensitive to the hormone.
• Exposure to high hormone concentrations can cause downregulation of cell receptors, making cells less sensitive to the hormone.

Hormone Regulation

• Hormones can downregulate or upregulate receptors for other hormones
  • Downregulation reduces the effectiveness of the second hormone.
  • Upregulation increases the effectiveness of the second hormone.
  • Permissiveness is the phenomenon where one hormone is required for another hormone to exert its full effect.

Control of Hormone Secretion

• Hormone secretion is controlled by three main factors:
  • Hormonal signals: hormones can stimulate or inhibit the release of other hormones.
  • Neuronal signals: the nervous system can directly regulate hormone secretion.
  • Plasma composition: alterations in the concentrations of ions or organic molecules can influence the secretion of certain hormones.
• It is possible for multiple regulatory systems to control the secretion of a single hormone.

### Thyroid Hormones

• The thyroid gland synthesizes and secretes thyroid hormones (T3 and T4).
• Synthesis requires the uptake of iodide from the plasma.
• Iodide is coupled with the amino acid tyrosine to form thyroid hormones.

### Control of Thyroid Hormone Secretion

• Thyroid hormone secretion is regulated by a negative feedback mechanism.
• This feedback loop is activated by low levels of T3 and T4 and low metabolic rate.

Actions of Thyroid Hormones

• Thyroid hormones significantly contribute to the regulation of:
  • Basal Metabolic Rate
  • Cardiovascular function
  • Growth and development
  • Nervous System function

Growth Hormone

• Growth hormone is a hormone that stimulates protein synthesis.
• It is produced and secreted by the pituitary gland.
• Growth hormone stimulates protein synthesis in many tissues, especially muscles.
• It increases the uptake of amino acids and the synthesis and activity of ribosomes.

Growth Hormone Secretion

• Growth hormone secretion is regulated by numerous factors.
• Secretion occurs in episodic bursts throughout the day.
• Secretion is low during the day, but bursts can be triggered by specific stimuli, such as exercise and sleep.
• The frequency of bursts can be affected by age, stress, and nutritional status.