Molecular Signaling Pathways

Receptors and Hormone Signaling

• JAKs (Janus kinases) and STAT (signal transducer and activator of transcription) are involved in hormone signaling, with examples including growth hormone and prolactin.
• Guanylyl cyclase receptors transmit messages, with an example being arterial natriuretic factor (ANF).

Intracellular Receptors

• Thyroid, steroid, and retinoic acid hormone receptors exist in soluble form inside cells, with hormones passing through the cell membrane by simple diffusion.
• The receptor-hormone complex is transported into the nucleus, binding to specific hormone response elements and stimulating gene transcription.

Regulation of Receptor Activity

• Desensitization occurs through decreased responsiveness to increased hormone amounts, reduced receptor numbers or affinity, downregulation, and covalent modification by phosphorylation.
• Upregulation increases target cell sensitivity, with examples including prolactin and angiotensine II.

Hormone Regulation

• Hormone amounts in blood circulation are controlled by synthesis, release, breakdown, and removal processes.
• The hypothalamic-pituitary regulatory system integrates messages from internal and external sensory receptors to control hormone production.
• Feedback control involves hormones released from target glands regulating production by changing hypothalamic and pituitary hormone secretion.

Biological Rhythms

• Biological rhythms refer to periodic biological events, with examples including circadian rhythms in pituitary hormone secretion.
• Oxytocin has a circadian rhythm and is released in response to suckling, neurogenic stimuli, and psychological stimuli, with inhibition by stressful situations.

Oxytocin

• Oxytocin has a half-life of 3-5 minutes and is rapidly degraded by oxytocinase.
• Pathologic conditions associated with oxytocin excess or deficiency are rare.

Arginine Vasopressin/Antidiuretic Hormone (ADH)

• ADH is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus.
• ADH regulates water balance and osmotic homeostasis by stimulating V2 receptors in the kidney, increasing water permeability and reabsorption.
• ADH secretion is modulated by changes in serum osmolality and intravascular volume, with detection by osmoreceptors in the anterior hypothalamus.

Syndrome of Inappropriate Secretion of ADH (SIADH)

• SIADH is characterized by euvolemic hypoosmolar hyponatremia with hyperosmolar urine.

Hypothalamus and Pituitary Gland

• The hypothalamus communicates with the anterior pituitary gland by secreting trophic hormones specific for each cell population.
• Prolactin (PRL) is produced by the lactotrophs of the pituitary gland, responsible for lactation initiation and maintenance.

Prolactin

• PRL secretion is normally kept low by dopamine produced by the hypothalamus.
• PRL is secreted in a circadian fashion, with highest levels during sleep and a nadir between 10 am and noon.
• Reference values for serum PRL are 1-25 ng/mL for women and 1-20 ng/mL for men.
• PRL levels are increased by physiologic and pathologic factors, as well as by medications.

Hyperprolactinemia

• Hyperprolactinemia leads to inhibition of GnRH secretion, manifesting as sexual dysfunction and infertility in both men and women.
• Pituitary adenomas are an important cause of hyperprolactinemia, with elevation of serum PRL levels correlating with the likelihood of a pituitary tumor.
• Hypothyroidism is another important cause of hyperprolactinemia, with thyroid hormone replacement therapy usually returning PRL levels to normal.

Hypoprolactinemia

• PRL deficiency can be seen with pituitary necrosis or infarction, and in some cases of pseudohypoparathyroidism.
• In women with complete PRL deficiency, menstrual disorders and infertility have been found.

Growth Hormone (GH)

• GH is a single-chain polypeptide synthesized, stored, and secreted by the somatotrophs of the pituitary gland in response to GHRH secretion by the hypothalamus.
• Somatostatin, also produced by the hypothalamus, inhibits GH synthesis and release.

This quiz covers different molecular signaling pathways, including JAK-STAT, guanylyl cyclase receptors, and intracellular receptors. Examples of signaling molecules include growth hormone, prolactin, and thyroid hormone.