Adrenal Gland Hormones

Adrenal Gland

• The adrenal gland has two main parts: the cortex and the medulla.

Adrenal Cortex

• The adrenal cortex has three zones which release hormones.
• The zona glomerulosa produces aldosterone which regulates sodium and potassium levels and also blood pressure.
• The zona fasciculata produces cortisol, which increases blood glucose levels and suppresses the immune system.
• The zona reticularis produces androgens (DHEA), which are minor sex steroids, especially in females.

Adrenal Medulla

• Chromaffin cells, which are modified sympathetic neurons, synthesize catecholamines from tyrosine.
• Synthesis steps entail: tyrosine converted to L-DOPA, then to dopamine, then norepinephrine and finally to epinephrine via PNMT(an enzyme stimulated by cortisol).
• Catecholamines are stored in chromaffin granules with ATP, calcium, and chromogranins.
• Acetylcholine (ACh) from sympathetic nerves triggers release, which activates nicotinic receptors, causing depolarization, where calcium influx leads to exocytosis of vesicles.
• Epinephrine increases heart rate, dilates airways, and increases glucose to mobilize energy.
• Norepinephrine increases blood pressure by vasoconstriction.
• Storage permits rapid release into the bloodstream when needed.
• Release occurs rapidly during the fight-or-flight response, increasing alertness, metabolism, and blood flow to muscles, as well as digestive activity.

Stress Response

• The body goes through short-term and long-term responses when dealing with stress.

Short-term Stress Response

• Epinephrine and norepinephrine(from the adrenal medulla) elicit;
• Increased heart rate, stroke volume, and blood pressure which causes increased blood flow to skeletal muscles.
• Bronchodilation which increases oxygen intake.
• Glycogenolysis which increases blood glucose and free fatty acids.
• Digestion and urine output decrease
• Causes increased alertness and arousal

Long-term Stress Response

• Cortisol(zona fasciculata, adrenal cortex): Stimulates gluconeogenesis, increases blood glucose, promotes protein and fat breakdown for energy, suppresses immune and inflammatory responses.
• Aldosterone which increases sodium and water reabsorption in the kidneys, helps to maintain and increase blood volume and pressure.

Pancreas Structure

• The pancreas has exocrine and endocrine cell types.

Exocrine Cell Types

• Acinar cells secrete digestive enzymes (amylase, lipase, proteases) into the pancreatic duct and further into the small intestine.
• Ductal cells secrete bicarbonate to neutralize gastric acid.

Endocrine Cell Types

• Alpha (α) cells secrete glucagon, which increases blood glucose via glycogenolysis and gluconeogenesis.
• Beta (β) cells secrete insulin, which decreases blood glucose by promoting uptake and storage.
• Delta (δ) cells secrete somatostatin, which inhibits insulin, glucagon, and GH.
• PP (F) cells secrete pancreatic polypeptide, which regulates exocrine & endocrine secretions and GI motility.
• Epsilon (ε) cells secrete ghrelin to regulate appetite, but play a minor role in the pancreas.

Glucose Homeostasis

• Glucose homeostasis includes fasting and being in a high blood glucose state

• During fasting:

  • Blood glucose levels are low.
  • Alpha cells in the islets of Langerhans are triggered.
  • Glucagon is released
  • This increases glycogenolysis and gluconeogenesis, which increases the glucose released.
  • Alternative fuels such as fatty acids and ketones are used, reducing glucose uptake.
  • Causes blood glucose levels to increase back toward normal.

• Elevated blood glucose levels

  • Blood glucose levels are high.
  • Beta cells in the islets of Langerhans are triggered.
  • Insulin is secreted.
  • This increases glycogen synthesis and glucose uptake leading to glucose being stored.
  • Glucose uptake increases especially in the muscle and fat cells.
  • Causes blood glucose levels to decrease back toward normal.

Insulin secretion mechanism in β-cells

• Glucose enters β-cells via GLUT2 transporters (facilitated diffusion), which is proportional to blood glucose levels.
• Glucose is metabolized through glycolysis and the TCA cycle, which leads to increased ATP production.
• The ATP/ADP ratio increases, causing ATP-sensitive K+ channels to close.
• Membrane depolarization occurs due to decreased K+ efflux.
• Voltage-gated Ca2+ channels open, causing calcium influx into the β-cell.
• Intracellular Ca2+ increases, triggering exocytosis of insulin-containing vesicles.
• Insulin is secreted into the bloodstream and acts on target tissues (muscle, fat, liver) to lower blood glucose.

Insulin Uptake Mechanism by the Muscles

• Insulin uptake mechanism varies between working and resting muscles

Working Muscles

• Insulin-independent mechanism is triggered
• Muscle contractions stimulate translocation of GLUT4 transporters to the cell membrane.
• Glucose enters muscle cells without insulin via GLUT4
• This is important during exercise or physical activity

Resting Muscles

• Insulin-dependent mechanism is triggered
• Insulin binds to insulin receptors on muscle cell membranes.
• A signaling cascade is triggered (via IRS, PI3K, Akt pathway).
• Promotes GLUT4 translocation to the membrane, increasing glucose uptake.
• This occurs after meals when insulin is high

Glucose Transporters & Insulin

• Some tissues, but not all of them, require insulin for glucose uptake

Tissues Requiring Insulin for Glucose Uptake

• Skeletal muscle (at rest)
• Adipose tissue: Use GLUT4 transporters (insulin-dependent)

Tissues NOT Requiring Insulin for Glucose Uptake

• Brain (always insulin-independent; uses GLUT1 and GLUT3)
• Liver (GLUT2 - bidirectional transport, not insulin-dependent)
• Red blood cells (RBCs) (GLUT1)
• Kidneys and intestine (some parts)
• Exercising skeletal muscle (insulin-independent via muscle contraction)

Glucagon Secretion

• Glucagon secretions can be stimulatory or inhibitory

Stimulatory Factors

• Low blood glucose (hypoglycemia)
• Amino acids (especially arginine and alanine)
• Exercise
• Sympathetic stimulation (via norepinephrine/epinephrine)
• Fasting

Inhibitory Factors

• High blood glucose (hyperglycemia)
• Insulin (paracrine inhibition from β-cells)
• Somatostatin (from 6-cells)
• Fatty acids and ketones (inhibit glucagon when energy is sufficient)

HPG Axis

• The Hypothalamus-Pituitary-Gonad (HPG) axis, regulates reproduction and development

• Hypothalamus:

  • Secretes gonadotropin-releasing hormone (GnRH).

• Anterior pituitary (hypophysis):

  • Secretes LH: releases of T.
  • Secretes FSH: mitosis of Leydig triggers releases of a bunch of hormones.

• Gonads:

  • Secretes Testosterone which is taken by Sertoli cells & converted to E and thereby Stimulates meiotic division of spermatocytes & affects development of 2° sexual tissues.
  • Secretes Inhibin - paracrine and endocrine stimulation to suppresses secretion of FSH.

Endocrine Cells in the Gonads

• Within a time-frame LH and FSH dependant gonads perform cellular and hormonal secretion

FHS Dependant

• Time: 1-3hrs
• Male: Sertoli cells (Nurse cells to seminiferous tubules, supporting spermatogonia to initiate spermatogenesis and also perform exocrine: androgen-binding (ABP) with endocrine: insulin + MIH/AMH secretion)
• Female: Granulosa cells secreting Estrogen.

LH Dependant

• Time: 30 mins
• Male: Leydig cells (in-between Seminiferous tubules, secreting Testosterone (+ androsten) and performing mitosis.
• Female: Theca cells secreting androgens that converts into E by Granulosa cells.

Spermatogenesis: 4 Steps

• Spermatogenesis has 4 steps:

• Proliferation:

  • Step 1 entails the mitosis of spermatogonia (stem cells)
  • This produces 1º spermatocytes (2n, 46 chromosomes) and needs testosterone

• Meiosis x2:

  • Spermatocytes become spermatids (1n, 23 chrom), regulated by FSH and testosterone

• Spermiogenesis: -Maturation + development into Spermatozoa/sperm

• Spermiation:

  • Release of mature sperm

Oogenesis Summaries

• Oogenesis is a form of egg development
• Stages entails detailed meitoic events

Stages and Meiotic Events

• Fetal period: Oogonium turns to mitosis (Chromosomal Complement of 2n, 2c)
• Before/At birth: Primary oocyte begins meiosis I (Chromosomal Complement of 2n, 4c)
• After birth: Arrested in diplotene (prophase I) (Chromosomal Complement of 2n, 4c)
• After puberty: Meiosis resumes; meiosis I completes (Chromosomal Complement of 1n, 2c)
• Ovulation: Secondary oocyte arrested in metaphase II (Chromosomal Complement of 1n, 2c)
• Fertilization: Meiosis II completed (Chromosomal Complement of 1n, 1c + sperm)
• Summary: Meiosis begins before birth and arrests twice - Meiosis II thatis completed at ovulation (LH surge) -

Folliculogenesis Summary

• Folliculogenesis entails hormonal balances at its different stages

• Primordial: Small oocyte + pre-granulosa cells (Gonadotropin-independent).

• Activated Primordial: Cuboidal granulosa cells (Independent).

• Primary: Zona pellucida forms (Independent)

• Secondary: Multiple granulosa layers + theca cells (Independent)

• Early Antral: Antrum begins forming (Transition to FSH-dependence).

• Antral/Dominant: Large antrum; cumulus cells; low O2 (FSH & LH dependent).

• Ovulation: Cumulus-oocyte complex released (Triggered by LH surge).

• Summary: Early growth is hormone-independent - Antrum formation = FSH dependence - Only dominant cells.

Ovarian & Uterine Cycles

• The ovarian and uterine cycles are interconnected and regulated by hormones

Ovarian Cycle

• Follicular Phase: Days 1-14, where FSH stimulates follicle development and follicles secrete estrogen.
• Ovulation: Day 14, where a surge in LH triggers ovulation and release of the secondary oocyte.
• Luteal Phase: Days 15-28, where the ruptured follicle becomes the corpus luteum and secretes progesterone.

Uterine Cycle

• Menstrual Phase: Days 1-5, where shedding of the endometrial lining occurs due to a drop in progesterone.
• Proliferative Phase: Days 6-14, where estrogen from follicles promotes endometrial growth.
• Secretory Phase: Days 15-28, where progesterone from the corpus luteum thickens and vascularizes the lining.

Hormonal Control of Lactation

• The hormonal control of lactation includes:
• Hypothalamus
• Anterior Pituitary
• Posterior Pituitary
• Secretory cells in the alveoli of the breast
• Smooth muscles of the breast
• Mechanoreceptors in the nipple

Hormonal Control of Lactation: Steps

• Mechanoreceptors in the nipple detect suckling and send signals to the hypothalamus.
• The hypothalamus (first activation) stimulates both the anterior and posterior pituitary.
• The posterior pituitary releases oxytocin, which targets smooth muscle in the breast and causes milk ejection.
• Smooth muscles then contract to eject milk from alveoli.
• The anterior pituitary releases prolactin, which targets secretory cells in alveoli.
• Secretory cells of alveoli are stimulated by prolactin to produce milk.
• Hypothalamus (feedback loop) continues the cycle as long as suckling persists.

Puberty

• Puberty is activated due to hormonal processes

• Activation of the HPG axis (hypothalamic-pituitary-gonadal axis)

• Elevated GnRH causes elevated FSH and LH from the anterior pituitary

• FSH & LH stimulate the gonads leading to increased sex steroid production (estrogen/testosterone)

• The development of secondary sexual characteristics is marked

• The onset of gametogenesis occurs

• Menarche in females and spermatogenesis in males.

Menopause

• Menopause marks a point in women's lives where reproductive abilities ends due to hormonal and cellular deterioration in sexual organs
• Permanent cessation of menstruation occurs due to ovarian follicle depletion.
• Estrogen and progesterone levels decline
• Loss of negative feedback that causes elevated GnRH, FSH, and LH
• Symptoms: hot flashes, mood changes, bone loss, vaginal dryness.
• Marks the end of reproductive capacity in females.