Hormone Signaling and Types

Endocrine, Paracrine, and Autocrine Signaling

• Endocrine signaling involves hormones secreted into the bloodstream to affect distant target cells.
• Paracrine signaling affects nearby cells.
• Autocrine signaling affects the same cell that secretes the hormone.

General Effects of Hormones

• Hormones can alter cell activity by changing membrane permeability
• Hormones activate or deactivate enzymes, influence protein synthesis, affect metabolic pathways
• Hormones induce secretory activity

Peptide Hormones

• Peptide hormones are made of amino acids.
• Peptide hormones cannot enter the cell directly
• Peptide hormones interact with receptors on the cell surface.
• Peptide hormones are generally not long-lasting.
• Peptide hormones travel freely in the bloodstream.
• Examples of peptide hormones: insulin, glucagon, growth hormone, prolactin, and oxytocin.

Steroid Hormones

• Steroid hormones are derived from cholesterol.
• Steroid hormones can enter the cell.
• Steroid hormones interact with receptors inside the cell.
• Steroid hormones tend to have long-lasting effects.
• Steroid hormones require transport proteins to travel in the bloodstream.
• Examples of steroid hormones: cortisol, aldosterone, testosterone.

Amine Hormones

• Amine hormones are derived from amino acids like tyrosine and tryptophan.
• Some amine hormones can enter cells; others cannot.
• Amine hormones interact with cell surface or intracellular receptors, depending on the specific hormone.
• Amine hormones vary in how long their effects last.
• Amine hormones travel in the bloodstream either freely or bound to transport proteins.
• Examples of amine hormones: epinephrine and norepinephrine.

Hormone-Receptor Interaction

• A hormone interacts with a receptor based on the receptor's binding site and the hormone's shape.

G-Protein Coupled Receptors (GPCRs)

• GPCRs transmit hormonal signals by activating intracellular signaling pathways through G proteins.

Intracellular Signaling Cascades Linked to GPCRs

• Three intracellular signaling cascades linked to G-protein coupled receptors: cAMP, IP3/DAG, and arachidonic acid.

cAMP

• cAMP is made from ATP.
• cAMP activates protein kinases, influencing various cellular processes.

PIP2

• PIP2 is converted into IP3 and DAG.
• The enzyme phospholipase converts PIP2 into IP3 and DAG.

IP3 Effects

• IP3 causes the release of calcium from intracellular stores.

DAG Effects

• DAG activates protein kinase C.

Protein Kinase Activation

• Activation of a protein kinase influences cell function by phosphorylating other proteins, altering their activity.

Hormones Binding to Nuclear Receptors

• Steroid and thyroid hormones bind to nuclear receptors.

Nuclear Hormone Receptors

• Nuclear hormone receptors commonly regulate gene transcription.

Factors Determining Hormone Potency

• Hormone potency is determined by receptor affinity, hormone concentration, and receptor sensitivity.

Hormone Signal Amplification

• Hormone signal amplification involves a cascade where one hormone molecule activates multiple enzymes, leading to a large cellular effect.
• The benefit of hormone signal amplification to the cell includes a greater response with only a small amount of hormone

Hormonal Feedback

• Positive hormonal feedback amplifies a response.
• Negative hormonal feedback reduces a response.

Receptor Downregulation

• Receptor downregulation occurs through decreased receptor synthesis, increased receptor degradation, or receptor internalization.

Methods of Hormone Release

• Three methods of hormone release: hormonal, humoral, and neural.
  • Hormonal release: one hormone causes the release of another hormone
  • Humoral release: in response to changing levels of ions or nutrients in the blood
  • Neural release in response to nervous stimulation

Pituitary and Hypothalamus Location

• The pituitary and hypothalamus are located in the brain.
• The pituitary is connected to the hypothalamus by the pituitary stalk.

Pituitary Lobes

• Pituitary lobes: anterior pituitary (adenohypophysis) and posterior pituitary (neurohypophysis).
  • The anterior pituitary is comprised of glandular tissue.
  • The posterior pituitary is comprised of neural tissue.

Hypothalamus Regulation of Pituitary Secretions

• The hypothalamus regulates pituitary secretions through:
  • Hormonal signals to the anterior pituitary.
  • Direct neural connections to the posterior pituitary.

Anterior Pituitary Hormones

• Five hormones of the anterior pituitary include:
  • Growth hormone (GH), produced by somatotrophs, target organ: liver, stimulated by GHRH.
  • Prolactin (PRL), produced by lactotrophs, target organ: mammary glands, stimulated by TRH.
  • Adrenocorticotropic hormone (ACTH), produced by corticotrophs, target organ: adrenal cortex, stimulated by CRH.
  • Thyroid-stimulating hormone (TSH), produced by thyrotrophs, target organ: thyroid, stimulated by TRH.
  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), produced by gonadotrophs, target organ: ovaries/testes, stimulated by GnRH.

Posterior Pituitary Hormones

• Two hormones secreted from the posterior pituitary:
  • Oxytocin
  • Vasopressin (ADH)

Direct Actions of Growth Hormone

• Direct actions of growth hormone: increased lipolysis.

Indirect Actions of Growth Hormone

• Indirect actions of growth hormone: increased bone and muscle growth via IGF-1.

IGF

• IGF (Insulin-like Growth Factor) is produced in the liver.

Feedback Regulation of Growth Hormone

• Growth hormone is regulated by negative feedback.
• High levels of GH and IGF-1 inhibit GHRH release and stimulate somatostatin release.

Factors Stimulating GH Release

• Factors stimulating GH release: exercise, stress, hypoglycemia, high amino acid levels, and sleep.

Factors Inhibiting GH Release

• Factors that inhibit GH release: hyperglycemia, high GH levels, high IGF-1 levels, somatostatin, and obesity.

Prolactin Activity

• Prolactin activity is highest during pregnancy and breastfeeding.

Major Target Organ for Prolactin

• The major target organ for prolactin is the mammary glands.

Oxytocin Importance

• Oxytocin is essential for procreation and continuation, as it stimulates uterine contractions during childbirth and milk ejection during breastfeeding.

Circulating Thyroid Hormone Forms

• The two forms of circulating thyroid hormone are:
  • T4 (thyroxine).
  • T3 (triiodothyronine).

Thyroid Gland Location

• The thyroid gland is located in the neck, anterior to the trachea.

Stimulating Thyroid Hormone Release

• TSH (thyroid-stimulating hormone) stimulates thyroid hormone release.

Thyroid Hormone Synthesis and Secretion

• Thyroid hormone synthesis and secretion:
  • Iodide is trapped, thyroglobulin is synthesized, iodide is oxidized, iodine is attached to thyroglobulin, iodinated tyrosines are coupled, thyroglobulin is endocytosed, and T4 and T3 are cleaved and released.

Thyroid Hormone Effects on Metabolism

• Thyroid hormone effects on metabolism: increased basal metabolic rate, heat production, and glucose metabolism.

Thyroid Hormone Effects on Cardiovascular Function

• Thyroid hormone effects on cardiovascular function: increased heart rate and contractility.
  • These effects are not always direct; some are due to increased metabolism.

Thyroid Hormone Effects on Gastrointestinal Function

• Thyroid hormone effects on gastrointestinal function: increased motility and secretion.

Physiological Changes with Hypothyroidism

• Physiological changes with hypothyroidism:
  • Decreased metabolic rate.
  • Weight gain.
  • Fatigue.
  • Cold intolerance.
  • Constipation.
  • Bradycardia.

Parathyroid Hormone vs. Calcitonin

• Parathyroid hormone increases blood calcium levels.
• Calcitonin decreases blood calcium levels.

Parathyroid Hormone and Calcitonin Secretion

• Parathyroid hormone is secreted from the parathyroid glands.
• Calcitonin is secreted from the thyroid gland.

Adrenal Glands Location

• The adrenal glands are located on top of the kidneys.

Adrenal Gland Divisions

• The adrenal gland divisions: adrenal cortex and adrenal medulla.

Hormones Produced in Adrenal Gland Regions

• Hormones produced in the differing regions of the adrenal glands:
  • Adrenal cortex produces mineralocorticoids, glucocorticoids, and gonadocorticoids.
  • Adrenal medulla produces epinephrine and norepinephrine.

Mineralocorticoids

• Mineralocorticoids regulate electrolyte balance
• An example is aldosterone.

Stimulating Aldosterone Release

• Aldosterone release is stimulated by:
  • Angiotensin II.
  • High potassium levels.
  • Low sodium levels.

Aldosterone Secretion Regulation

• Aldosterone secretion is regulated by the renin-angiotensin-aldosterone system (RAAS).

Glucocorticoids

• Glucocorticoids regulate glucose metabolism and inflammation.

Triggering Cortisol Secretion

• ACTH (adrenocorticotropic hormone) triggers cortisol secretion.

Cortisol Secretion Regulation

• Cortisol secretion is regulated by negative feedback on the hypothalamus and anterior pituitary.

Gonadocorticoids

• Gonadocorticoids are adrenal sex hormones.
• Gonadocorticoids supplement gonadal sex hormones.

Epinephrine Functions

• Epinephrine functions to mediate the "fight or flight" response.

Short Term Responses to Stress

• Short-term responses to stress are mediated by the sympathetic nervous system and epinephrine release.

Long-Term Responses to Stress

• Long-term responses to stress are mediated by cortisol.

Pancreas Functions

• The two functions of the pancreas: exocrine (digestion) and endocrine (hormone secretion).

Pancreatic Cells with Endocrine Properties

• Pancreatic cells with endocrine properties:
  • Alpha cells produce glucagon.
  • Beta cells produce insulin.
  • Delta cells produce somatostatin.
  • PP cells produce pancreatic polypeptide.
• These cells are located in the islets of Langerhans.

Maintaining Blood Glucose Levels

• Blood glucose levels are maintained by the balance of insulin and glucagon.

Stimulating Glucagon Secretion

• Glucagon secretion is stimulated by low blood glucose levels.

Glucagon Effects

• Glucagon effects on target cells: increased glycogenolysis and gluconeogenesis.

Glucagon Signaling Cascade

• Glucagon uses the cAMP signaling cascade.

Stimulating Insulin Secretion

• Insulin secretion is stimulated by high blood glucose levels.

Insulin Effects

• Insulin effects on target cells: increased glucose uptake, glycogenesis, and lipogenesis.

Insulin Signaling Pathways

• Insulin uses the PI3K/Akt and MAPK signaling pathways.

Diabetes Mellitus Cause

• Diabetes mellitus is caused by lack of insulin or insulin resistance.

Diabetes Mellitus Symptoms

• Diabetes mellitus causes: hyperglycemia, polyuria, polydipsia, and polyphagia.

Lack of Insulin Effects

• Lack of insulin effects on target cells: decreased glucose uptake, increased lipolysis, and increased proteolysis.

Pancreatic Tumor Effects

• A tumor in the pancreas can cause either hypo- or hyperglycemia, depending on the cells affected and the hormones released.

Reproductive Endocrine Organs

• The reproductive endocrine organs in men: testes.
• The reproductive endocrine organs in women: ovaries.

Sex Hormone Actions

• General actions of the sex hormones: development and maintenance of reproductive tissues, secondary sex characteristics, and reproductive behaviors.

Testosterone's Regulation of Reproductive Function in Men

• Testosterone stimulates sperm production, muscle synthesis, and bone growth.

Testosterone Secretion Regulation

• Testosterone secretion is regulated by negative feedback on the hypothalamus and anterior pituitary.

Hormones Regulating Testicular Function

• Hormones regulating testicular function: FSH, LH, and testosterone.

FSH's Role in Reproductive Function

• FSH stimulates sperm production in Sertoli cells.

LH's Role in Reproductive Function

• LH stimulates testosterone production in Leydig cells.

Secondary Sex Characteristics Influenced by Testosterone

• Secondary sex characteristics influenced by testosterone: facial hair, deep voice, and increased muscle mass.

Ovarian Cycle Phases

• The phases of the ovarian cycle:
  • Follicular phase: follicle growth and maturation.
  • Ovulation: release of the egg.
  • Luteal phase: formation and maintenance of the corpus luteum.

Gonadotropin Variation During the Ovarian Cycle

• Gonadotropins vary during the ovarian cycle.
• FSH peaks early in the follicular phase.
• LH surges before ovulation.

Gonadotropin Effects on Estrogen Secretion

• Gonadotropins stimulate estrogen secretion by the ovaries.

LH and FSH Secretion Regulation in Women

• LH and FSH secretion is regulated by negative and positive feedback from estrogen and progesterone.

Triggering Ovulation

• A surge of LH triggers ovulation.

Hormonal Changes Associated with the Uterine Cycle

• Hormonal changes associated with the uterine cycle: estrogen stimulates endometrial growth, and progesterone maintains the endometrium.

Extrauterine Effects of Estrogen

• Extrauterine effects of estrogen include: bone growth and cardiovascular protection.

Secondary Sex Characteristics Caused by Estrogen

• Secondary sex characteristics caused by estrogen: breast development, widening of the hips, and fat distribution.