The marine iguana (Amblyrhynchus cristatus)

Common Aspects of Neural and Endocrine Regulation

• APs are chemical events produced by diffusion of ions through neuron plasma membrane.

• Action of some hormones are accompanied by ion diffusion and electrical changes in the target cell.– Nerve axon boutons release NTs.– Some chemicals are secreted as hormones, and also are NTs.

• In order for either a NT or hormone to function in physiological regulation:– Target cell must have specific receptor proteins.– Combination of the regulatory molecule with its receptor proteins

must cause a specific sequence of changes.– There must be a mechanism to quickly turn off the action of a

regulator.

Endocrine Glands and Hormones

• Secrete biologically active molecules into the blood.– Lack ducts.

• Carry hormones to target cells that contain specific receptor proteins for that hormone.

• Target cells can respond in a specific fashion.

Endocrine Glands and Hormones (continued)

• Neurohormone:– Specialized neurons that secrete chemicals into the

blood rather than synaptic cleft.• Chemical secreted is called neurohormone.

• Hormones:– Affect metabolism of target organs.

• Help regulate total body metabolism, growth, and reproduction.

Chemical Classification of Hormones (continued)

• Glycoproteins:– Long polypeptides (>100) bound to 1 or more carbohydrate

(CHO) groups.• FSH and LH.

• Hormones can also be divided into:– Polar:

• H20 soluble.

– Nonpolar (lipophilic):• H20 insoluble.

– Can gain entry into target cells.– Steroid hormones and T4.

– Pineal gland secretes melatonin:• Has properties of both H20 soluble and lipophilic hormones.

Chemical Classification of Hormones (continued)

• Steroid hormones- lipid soluble– Synthesize from cholesterol

• Invertebrates--Molting hormone• Vertebrates– gonads and adrenal cortex

• Peptide and protein hormones-transported via carrier proteins– Invertebrates– gamete-shedding hormones– Vertebrates-- ADH, insulin, growth hormone

• Amine hormones– – Melatonin, catecholamines, and iodothyronines

• Synergistic:– Two hormones work together to produce a

result.– Additive:

• Each hormone separately produces response, together at same concentrations stimulate even greater effect.

– NE and Epi.

– Complementary:• Each hormone stimulates different step in the

process.– FSH and testosterone.

Hormonal Interactions

Hormonal Interactions (continued)

– Permissive effects:• Hormone enhances the responsiveness of a

target organ to second hormone.– Increases the activity of a second hormone.

» Prior exposure of uterus to estrogen induces formation of receptors for progesterone.

– Antagonistic effects:• Action of one hormone antagonizes the effects

of another.– Insulin and glucagon.

Effects of [Hormone] on Tissue Response

• [Hormone] in blood reflects the rate of secretion.

• Half-life: – Time required for the blood [hormone] to be reduced

to ½ reference level.• Minutes to days.

• Normal tissue responses are produced only when [hormone] are present within physiological range.

• Varying [hormone] within normal, physiological range can affect the responsiveness of target cells.

Effects of [Hormone] on Tissue Response (continued)

• Priming effect (upregulation):– Increase number of receptors formed on target

cells in response to particular hormone.– Greater response by the target cell.

• Desensitization (downregulation):– Prolonged exposure to high [polypeptide

hormone].• Subsequent exposure to the same [hormone] produces

less response.– Decrease in number of receptors on target cells.

» Insulin in adipose cells.

– Pulsatile secretion may prevent downregulation.

Mechanisms of Hormone Action

• Hormones of same chemical class have similar mechanisms of action.– Similarities include:

• Location of cellular receptor proteins depends on the chemical nature of the hormone.

• Events that occur in the target cells.

• To respond to a hormone:– Target cell must have specific receptors for

that hormone (specificity).• Hormones exhibit:

– Affinity (bind to receptors with high bond strength).– Saturation (low capacity of receptors).

Hormones That Bind to Nuclear Receptor Proteins

• Lipophilic steroid and thyroid hormones are attached to plasma carrier proteins.– Hormones dissociate

from carrier proteins to pass through lipid component of the target plasma membrane.

• Receptors for the lipophilic hormones are known as nuclear hormone receptors.

Nuclear Hormone Receptors

• Steroid receptors are located in cytoplasm and in the nucleus.

• Function within cell to activate genetic transcription.– Messenger RNA directs synthesis of specific enzyme

proteins that change metabolism.

• Each nuclear hormone receptor has 2 regions:– A ligand (hormone)-binding domain.– DNA-binding domain.

• Receptor must be activated by binding to hormone before binding to specific region of DNA called HRE (hormone responsive element).– Located adjacent to gene that will be transcribed.

Mechanisms of Steroid Hormone Action

• Cytoplasmic receptor binds to steroid hormone.

• Translocates to nucleus.• DNA-binding domain

binds to specific HRE of the DNA.

• Dimerization occurs.– Process of 2 receptor units

coming together at the 2 half-sites.

• Stimulates transcription of particular genes.

Hormones That Use 2nd Messengers

• Hormones cannot pass through plasma membrane use 2nd messengers.– Catecholamine, polypeptide, and

glycoprotein hormones bind to receptor proteins on the target plasma membrane.

• Actions are mediated by 2nd messengers (signal-transduction mechanisms).– Extracellular hormones are transduced

into intracellular 2nd messengers.

Adenylate Cyclase-cAMP (continued)

• Phosphorylates enzymes within the cell to produce hormone’s effects.

• Modulates activity of enzymes present in the cell.

• Alters metabolism of the cell.

• cAMP inactivated by phosphodiesterase.– Hydrolyzes cAMP

to inactive fragments.

• Polypeptide or glycoprotein hormone binds to receptor protein causing dissociation of a subunit of G-protein.

• G-protein subunit binds to and activates adenylate cyclase.

• ATP cAMP + PPi • cAMP attaches to inhibitory subunit of

protein kinase.• Inhibitory subunit dissociates and

activates protein kinase.

Adenylate Cyclase-cAMP

Synthesis, storage, and release of hormones

• Peptide hormones– Synthesized by transcription of DNA,

translation and post-translational processing

• Steroid hormones– Synthesized from cholesterol

– Not stored, synthesize on demand

– Secreted by diffusion through cell membrane

Pituitary Gland

• Pituitary gland is located in the diencephalon.

• Structurally and functionally divided into:– Anterior lobe.– Posterior lobe.

The mammalian pituitary gland

• Pars nervosa- posterior pituitary– Contains terminals of axons – Secretory cells located in

hypothalamus

• Anterior pituitary– Nonneural endocrine cells– Secretion controlled by hypothalamo-

hypophyseal portal system– Separate populations of cells secrete

different hormones

Hypothalamic Control of Posterior Pituitary

• Hypothalamus neuron cell bodies produce:– ADH: supraoptic

nuclei.– Oxytocin:

paraventricular nuclei.

• Transported along the hypothalamo-hypophyseal tract.

• Stored in posterior pituitary.

• Release controlled by neuroendocrine reflexes.

Figure 14.6 The vertebrate pituitary gland has two parts (Part 1)

Pituitary Hormones (continued)

• Posterior pituitary:– Stores and releases 2 hormones that are

produced in the hypothalamus:• Antidiuretic hormone (ADH/vasopressin):

– Promotes the retention of H20 by the kidneys.» Less H20 is excreted in the urine.

• Oxytocin:– Stimulates contractions of the uterus during parturition.– Stimulates contractions of the mammary gland alveoli.

» Milk-ejection reflex.

• Posterior pituitary(neurohypophysis):– Formed by downgrowth of the brain

during fetal development.– Is in contact with the infundibulum.

• Nerve fibers extend through the infundibulum.

• Anterior pituitary:– Adenohypophysis– Derived from a pouch of epithelial tissue

that migrates upward from the mouth.

Pituitary Gland (continued)

Pituitary Hormones

• Anterior Pituitary:– Trophic effects:

• High blood [hormone] causes target organ to hypertrophy.

• Low blood [hormone] causes target organ to atrophy.

Hypothalamic Control of the Anterior Pituitary

• Hormonal control rather than neural.

• Hypothalamus neurons synthesize releasing and inhibiting hormones.

• Hormones are transported to axon endings of median eminence.

• Hormones secreted into the hypothalamo-hypophyseal portal system regulate the secretions of the anterior pituitary

Figure 14.6 The vertebrate pituitary gland has two parts (Part 2)

Figure 14.6 The vertebrate pituitary gland has two parts (Part 3)

Figure 14.6 The vertebrate pituitary gland has two parts (Part 4)

Figure 14.6 The vertebrate pituitary gland has two parts (Part 5)

• Anterior pituitary and hypothalamic secretions are controlled by the target organs they regulate.– Secretions are controlled by negative feedback

inhibition by target gland hormones.

• Negative feedback at 2 levels:– The target gland hormone can act on the

hypothalamus and inhibit secretion of releasing hormones.

– The target gland hormone can act on the anterior pituitary and inhibit response to the releasing hormone.

Feedback Control of the Anterior Pituitary

Feedback Control of the Anterior Pituitary (continued)

• Short feedback loop:– Retrograde transport of

blood from anterior pituitary to the hypothalamus.

• Hormone released by anterior pituitary inhibits secretion of releasing hormone.

• Positive feedback effect:– During the menstrual

cycle, estrogen stimulates “LH surge.”

Higher Brain Function and Pituitary Secretion

• Axis:– Relationship between anterior pituitary and a

particular target gland.• Pituitary-gonad axis.

• Hypothalamus receives input from higher brain centers.– Psychological stress affects:

• Circadian rhythms.• Menstrual cycle.

Figure 14.7 The adrenal gland consists of an inner medulla and an outer cortex

Figure 14.8 Both hormonal and neural mechanisms modulate the action of the HPA axis

Figure 14.9 Interactions of insulin, glucagon, and epinephrine

Figure 14.10 The mammalian stress response (Part 1)

Figure 14.10 The mammalian stress response (Part 2)

Figure 14.11 The CNS and the immune system interact during the stress response

• Cytokines released from certain cells of the immune system– Binds with specific receptor molecules– Travel in the blood to hypothalamus

• Stimulate CRH neurosecretory cells– Resulting in the physiological responses of

the HPA axis• Helps fight infection

– Glucocorticoids inhibit the production of agents that cause inflammation-modulating the immune response

The CNS and the immune system interact during the stress response

• Insulin secreted when nutrients molecules are abundant– Hypoglycemic effect- promote uptake of nutrients– Inhibit degradation of glycogen, lipids and proteins

• Glucagon secreted when glucose level is low– Hyperglycemic effect- stimulate break down of

glycogen, triglyceride molecules– Forms glucose from noncarbohydrate sources

• Growth hormone, glucocorticoids, epinephrine, thyroid hormones play permissive and synergistic roles in nutrient metabolism

Endocrine control of nutrient metabolism in mammals

Figure 14.12 Hormone & nutrient levels in blood of healthy humans before & after a meal (Part 1)

Figure 14.12 Hormone & nutrient levels in blood of healthy humans before & after a meal (Part 2)

Figure 14.13 The action of an antidiuretic hormone (Part 1)

Figure 14.13 The action of an antidiuretic hormone (Part 2)

Figure 14.14 The renin–angiotensin–aldosterone system (Part 1)

Figure 14.14 The renin–angiotensin–aldosterone system (Part 2)

• Vasopressin (ADH)- peptide neurohormone– Stimulate conservation of water

• Aldosterone– Stimulate conservation of Na+– Part of renin-angiotensin-aldosterone

system

• ANP- atrial natriuretic peptide– Stimulate the excretion of Na+ and water

Endocrine control of salt and water balance in vertebrates

Figure 14.15 Chemical messengers act over short, intermediate, and long distances

Figure 14.16 Two types of metamorphosis

Figure 14.17 The silkworm Bombyx mori goes through holometabolous development

• Three hormones control metamorphosis:– Prothoracicotropic hormone – PTTH– Ecdysone– Juvenile hormone JH

• Secreted by nonneural endocrine cells• Prevents metamorphosis in the adult form• In adult, stimulates sex-attractant pheromones

• Additional hormones– Bursicaon – darkening and hardening of the cuticle– Eclosion hormone (EH)– Pre-ecdysis triggering hormone (PETH) – Ecdysis triggering hormone (ETH)

– Control stereotyped movements during ecdysis

Insect metamorphosis – part 1

• Convergent evolution of endocrine and neuroendocrine functions between vertebrate and invertebrate animals

• Hemimetabolous insects go through gradual metamorphosis

• Holometabolous insects go through complete metamorphosis

• Environmental and behavioral signals mediated by the nervous system initiate molting

Insect metamorphosis part 2

• Neuroendocrine cells in the brain secrete PTTH

• Stimulates secretion of ecdysone from the prothoracic glands

• Ecdysone is converted to 20-hydroxyecdysone by peripheral activation

• Epidermis secrete enzymes required for molting process

Insect metamorphosis – part 3

Figure 14.19 Endocrine & neuroendocrine structures involved in control of insect metamorphosis (1)

Figure 14.19 Endocrine & neuroendocrine structures involved in control of insect metamorphosis (2)