Non-Reproductive Endocrinology

IV. Response to Hormone by Target Cell

A. Mechanisms of Stimulation

1. Hormones which can’t enter target cells

a. Specific membrane receptors are necessary for hormone to act on cell.

- receptors are integral membrane proteins

- binding of receptor by hormone is specific and reversible

b. Require “second messengers” (a term coined by Earl Sutherland)

- e.g. cAMP, cGMP and Ca²⁺

c. G-protein Coupled Receptors

d. Examples of differing responses of cells to cAMP

- Thyroid cells – TSH à cAMP prodn. à activation of iodine pump, tyrosine iodination, secretion of thyroid hormones

- Heart – Norepinephrine à cAMP prodn à activation of channels

- ACh à cGMP prodn à antagonizes cAMP effects

e. As long as hormone is bound to receptor (in general) second messenger system will be stimulated. Signaling is terminated when hormone levels fall, and hormone dissociates from the receptor, and/or hormone is degraded.

- Deactivation of second messengers

- Ca²⁺ is pumped out of the cell or into storage organelles.

- cAMP is degraded by phosphodiesterases or is effluxed (FX of caffeine and theophylline)

f. In some cases, hormones are endocytosed along with receptors. Then the hormone is detached from the receptor in vesicles in the cells, and receptor down-regulation or receptor recycling can occur.

2. Hormones which can enter cells

a. Hormones are carried in the blood by carrier proteins.

b. Generally enter cell by simple diffusion.

c. Target cell possesses cytoplasmic receptors or nuclear receptors.

d. If receptors aren’t already in the nucleus, they’re transported their where they function as transcription factors.

V. Neurosecretory sytem – The common link between the nervous system and the endocrine system.

A. Neurosecretory neurons

1. General Characteristics

a. Release chemical secretions directly into circulation instead of at synaptic cleft. “Glandular neurons.” (see figure 8-8B in Eckert Animal Physiology)

b. Expands influence of nervous system

c. NS can now influence cells at great distance in a longer lasting, more general way.

d. Found in all animals

2. Operation

a. Receive neuronal inputs.

b. Excitable. Soma sums passive potentials; axon conducts slow APs. Soma makes and packages neurosecretory products (neurohormones).

c. Axon terminal is located on a capillary.

B. Organization

1. First order system

NSà (stim or inhib) target organ

2. Second order system

NS à (stim) target endocrine organ à (stim or inhib) target organ

3. Third order system

NS à (stim) target endocrine organ à(stim) target endocrine organ à (stim or inhib) target organ

- This third order system features negative feedback between the downstream target endocrine organs.

- Ultimately NS controls much of endocrine activity.

VI. Specific Endocrine Organs (see Table 8-1 8B in Eckert Animal Physiology)

A. Pituitary Gland (a.k.a. hypophysis)

1. Structure

a. Neurohypophysis

i. Derived from neuroectoderm

ii. Comprises pars nervosa (posterior pituitary) and median eminence

b. Adenohypophysis

i. Derived from epidermal ectoderm

ii. Anterior pituitary

- pars distalis (distal lobe) = major component

- pars intermedia (intermediate lobe) = minor component

- pars tuberalis (tuberal lobe) – minor component

c. Portal circulation – two capillary beds without a heart in between them

i. Median eminence = neurohemal organ. Neurons synapse on capillaries in capillary bed in median eminence.

ii. Capillaries converge to form venules.

iii. Venules branch to form second capillary bed in the anterior pituitary.

iv. Functional significance = ME neurons produce releasing and release-inhibiting hormones that act on endocrine cells in the anterior pituitary to cause it to release its hormones. (2^nd or 3^rd order system)

2. Functions

a. Neurohypophysis

i. osmoregulation – antidiuretic hormone (ADH)

- a.k.a. arginine vasopressin (AVP) in mammals and arginine vasotocin (AVT) in reptiles, fish and birds

- Stimulus: Hypothalamic neurons detect changes in plasma osmolarity; upon detection of increasing plasma osmolarity, they secrete ADH.

- Result: Conservation of water in terrestrial vertebrates. Kidneys are inhibited from producing urine. Epithelia becomes more permeable to water. This makes it easier for water to enter the body from the outside. This effect is evident in amphibia. (first order system)

ii. Reproductive – oxytocin (mammalian)

- a.k.a. arginine vasotocin (reptiles, fish and birds)

- Stimulus: Parturition or suckling

- Result: Contract smooth muscles of reproductive organs. Uterine contractions (parturition), oviduct contraction (egg laying) and milk ejection (suckling). Endocrine reflex arc associated with milk ejection.

b. Median Eminence

i. Regulate secretion of adenohypophyseal hormones through secretion of releasing or release-inhibiting hormones/factors

ii. Neurons whose endings are in the median eminence originate in hypothalamic nuclei. These neurons produce a variety of hormones including GHRH (2^nd order), corticotropin-releasing hormone, and TSH-releasing hormone (3^rd order systems) (see Table 9-2 in text)

c. Adenohypophysis – component cells can be classified into two histochemically distinct types: acidophils and basophils

i. Acidophils produce growth hormone and prolactin

- growth hormone: a.k.a. somatotropin.

- ~ 200 aa long.

- reg’d by GHRH and somatostatin

- direct FX: hyperglycemia through breakdown of fat. Protein synthesis and aa uptake

- indirect FX: increases long bone growth by causin secretion of somatomedins (peptide hormones) from liver.

- assoc’d abnormalities: dwarfism (no GH), gigantism (too much GH)

- prolactin

- reg’d by TRH (possibly) and dopamine

- FX – varied

- mammals: development of mammary glands and maintenance of lactation. Inhibition of fertility.

- birds: induces crop sac to make crop milk. Induces parental care, nest building, development of an incubation patch.

- reptiles, amphibians and fish: osmoregulatory. Some parental care. Some developmental FX.

ii. Basophils produce adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), melanocyte stimulating hormone (MSH), luteinizing hormone (LH), and follicle stimulating hormone (FSH). All but MSH operate on other endocrine glands.

- ACTH – stimulates secretion of steroid hormones by adrenal cortex. Inhibits synthesis and secretion of CRH.

- TSH – stimulates synthesis and secretion of thyroid hormones from thyroid gland.

- MSH – acts directly on pigment cells in the skin to increase the synthesis and dispersal of melanin.

- LH and FSH to be discussed later.

B. Adrenal Glands

1. Structure

a. Adrenal coretx – steroidogenic cells

b. adrenal medulla – chromaffin cells derived from sympathetic neurons. Functions as neurohemal organow hose secretion fo hormones is regulated by sumpathetic input. Synthesizes and secretes catecholamines norepinephrine and epinephrine. The ratio of NE to E is regulated by corticosteroids. Steroids stimulate production of the EZ that converts NE to E.

2. Function

a. Acute stress response. Stress activates SNS which stimulates release of epinephrine (mainly) from adrenal medulla. Epinephrine acts on ß-receptors to cause vasodilation in vessels in skeletal muscle. Norepinephrine acts on alpha-recpetors to cause vasoconstriction in vessels associated with gut. Epinephrine also causes hyperglycemia as glucose is mobilized from the liver and fat is broken down in adipose tissue.

b. Chronic Stress. Acts on adrenal cortex. Causes secretion of corticosteroids (e.g. cortisone).

i. Glucocorticoids primary effects – hyperglycemia through gluconeogenesis and glucose export from liver and lipolysis from adipose tissue.

ii. Secondary FX – suppress immune system and suppress inflammation.

C. Osmoregulation. Mineralocorticoids (e.g. aldosterone) act on kidneys to retain sodium and excrete potassium. These aren’t regulated by ACTH.

C. Thyroid Gland (found in all vertebrates)

1. Thyroid hormones

T3 (tri-iodothyronine)

T4 (tetra-iodothyronine; thyroxine)

2. Regulation – synthesized and released under control of TSH, which in turn is regulated by TRH.

3. Actions

a. Negative feedback control of TRH and TSH. In absence of thyroid hormones, goiter happens.

b. Metabolic fxns.

i. Calorogenesis via production of ATP through aerobic respiration and utilization of ATP, e.g. by membrane pumps synthesized under control of thyroid hormones.

ii. Hyperglycemia via glycogenolysis and gluconeogenesis in the liver. Also inhibits fat synthesis in adipocytes.

iii. Increased metabolic rate.

c. Sensitization to epinephrine due to increased expression of adrenergic receptors.

d. Growth and Development

i. Synergizes with GH to affect development and maturation. Essential for development of the nervous system. Deficiency leads to cretinism.

ii. Amphibian metamorphosis – transition from larva (tadpole) to adult stimulated by thyroid hormones and inhibited by prolactin.