Hormones cascade system

HORMONAL CASCADE SYSTEM INVOLVING HYPOTHALAMUS

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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HORMONES CASCADE SYSTEM Hormones Produced by the Major Hormone-Producing (i.e., Endocrine) Glands and Their Primary Functions Endocrine Gland

Hypothalamus

Hormone Corticotropin- releasing hormone (CRH)

Stimulates the pituitary to release adrenocorticotropic hormone (ACTH)

Gonadotropin-releasing hormone (GnRH) Thyrotropin-releasing hormone (TRH)

Stimulates the pituitary to release luteinizing hormone (LH) and folliclestimulating hormone (FSH) Stimulates the pituitary to release thyroid-stimulating hormone (TSH)

Growth hormone-releasing hormone(GHRH)

Stimulates the release of growth hormone (GH) from the pituitary

Somatostatin

Inhibits the release of GH from the pituitary Inhibits the release of prolactin from the pituitary

Dopamine

Anterior pituitary gland

Primary Hormone Function

ACTH

Stimulates the release of hormones from the adrenal cortex

LH

In women, stimulates the production of sex hormones (i.e.,estrogens) in the ovaries as well as during ovulation; in men, stimulates testosterone production in the testes

FSH

In women, stimulates follicle development; in men, stimulates sperm production

TSH

Stimulates the release of thyroid hormone

GH

Promotes the body’s growth and development Controls milk production (i.e., lactation)

Prolactin

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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Posterior pituitary gland #

Vasopressin

Helps control the body’s water and electrolyte levels

Oxytocin

Promotes uterine contraction during labor and activates milk ejection in nursing women Helps control carbohydrate, protein, and lipid metabolism; protects against stress Helps control the body’s water and electrolyte regulation

Cortisol Adrenal cortex

Testes

Aldosterone

Testosterone

Estrogen (produced by the follicle)

Stimulates development of the male reproductive organs, sperm production, and protein anabolism Stimulates development of the female reproductive organs

Progesterone (produced by the corpus luteum)

Prepares uterus for pregnancy and mammary glands for lactation

Thyroid hormone (i.e., thyroxine [T4] and triiodothyronine [T3])

Controls metabolic processes in all cells

Calcitonin

Helps control calcium metabolism (i.e., lowers calcium levels in the blood)

Ovaries

Thyroid gland

Parathyroid hormone Parathyroid gland (PTH) Insulin Pancreas Glucagon

Helps control calcium metabolism (i.e., increases calcium levels in the blood) Helps control carbohydrate metabolism (i.e., lowers blood sugar levels) Helps control carbohydrate metabolism (i.e., increases blood sugar levels)

# These hormones are produced in the hypothalamus but stored in and released from the posterior pituitary gland.

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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1. Hormonal cascade system: a. Hypothalamus to anterior pituitary to ultimate glands 

Signaling steps -

For many hormonal systems, pathway originates in brain using components that innervate hypothalamus

-

Hypothalamus responds by secreting specific releasing hormones (polypeptide hormones)

-

Releasing hormones transported through closed portal system to anterior pituitary; bind to membrane receptors and cause secretion of specific anterior pituitary hormones (polypeptide hormones)

-

Anterior pituitary hormones enter bloodstream and bind receptors in ultimate glands (such as thyroid gland, adrenal cortex, ovary, testes)

-

Ultimate glands secrete hormones into bloodstream; hormones bind to receptors on target tissues to generate systemic response



Amplification of signal- amount and stability of hormones increased at each step in pathway



Negative feedback- hormones inhibit previous steps in pathway when sufficient amounts are present

b. Posterior pituitary hormones: oxytocin and vasopressin 

Synthesized in cell bodies of hypothalamic neurons



Carried down nerve fibers along with stabilizing proteins neurophysins



Stored in posterior pituitary until releasing signal present

c. Major hormones of anterior pituitary 

Thyrotropin (TSH): acts on thyroid follicle cells to bring about release of T4 and T3



Luteinizing hormone (LH): acts on Leydig cells of testis to increase testosterone synthesis; acts on corpus luteum of ovary to increase progesterone synthesis

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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

Follicle-stimulating hormone (FSH): acts on Sertoli cells of seminiferous tubule to promote spermatogenesis; acts on ovarian follicles to stimulate maturation of ovum and production of estradiol



Adrenocorticotropic hormone (ACTH): acts on cells in the adrenal cortex to increase cortisol (glucocorticoids) synthesis



Growth hormone (GH)



-Endorphin



Prolactin (PRL)



Melanocyte-stimulating hormone (MSH)

2. Synthesis of peptide hormones a. Multiple hormones can be encoded from one gene 

Gene product cleaved into multiple hormones; formation of particular cleavage products regulated by cell type



For example, proopiomelanocortin is precursor polypeptide for eight hormones

b. Other genes for hormones encode only one hormone

3. Thyroid hormone a. Synthesis 

Thyroid gland concentrates iodide from blood



Thyroglobulin is large protein; iodination of tyrosine residues produces monoiodotyrosine, diiodotyrosine, T3, and T4 as part of thyroglobin thyroid follicles



Endocytosis of throglobulin by epithelial cells followed by its proteolysis release T3 and T4 (active hormones) into bloodstream

b. Thyroid hormone affects many different cell types

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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4. Epinephrine a. Synthesis 

Synthesized in adrenal medulla



Derived from tyrosine or phenylalanine; norepinephrine synthesized first through series of reactions including several hydroxylations



Norepinephrine converted to epinephrine by phenylethanolamine Nmethyltransferase (PNMT)

b. Regulation of synthesis and release 

Neuronal control- acetylcholine stimulates exocytosis of granules that contain epinephrine



Glucocorticoids secreted from adrenal cortex induce key enzyme (PMNT) for synthesis of epinephrine

c. Acts on hepatocytes to increase blood glucose levels; vascular smooth muscle cells to cause contraction and increase blood pressure

5. Steroid hormones a. Most secreted from adrenal cortex, ovary and testes; synthesis induced by peptide hormones, most released from pituitary b. Derived from cholesterol; all have cyclopentanoperhydrophenanthrene nucleus with various modifications c. Bind to nuclear receptors that act as transcription factors regulated by ligand binding d. Biosynthesis 

All begin with cholesterol side chain cleavage to form 5-pregnenolone; occurs in mitochondria



Subsequent modifications occur in mitochondria, ER, and cytosol to produce specific steroids



Cytochrome P450's -

Large family of enzymes

-

Involved in initial side chain cleavage and subsequent hydroxylations

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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-

General reaction: NADPH + H+ +O2 + Sub-H → NADP+ + H2O + SubOH

-

Oxygen atom from O2 incorporated into steroid substrate as OH; electrons donated by NADPH

e. Control of steroid synthesis: activation of cell surface receptor results in stimulating conversion of cholesterol to steroids

Steroid

Hormone-producing Structure

Signal for Steroid Hormone Signal for Steroid Synthesis Structure

Hormone

Cortisol

Adrenal cortex

ACTH

Aldosterone

Adrenal cortex

Angiotensin II/III

Testosterone

Leydig cell

LH

Estradiol

Ovarian follicle

FSH

Progesterone

Corpus luteum

LH

1,25(OH)2 D3

Kidney

Parathyroid hormone (PTH)

f. Defects in steroid hormone synthesis: can be caused by an enzyme deficiency; for example, adrenal hyperplasia caused by 21-hydroxylase deficiency 

21-hydroxylase

deficiency causes lack of synthesis of cortisol and

aldosterone and buildup of androgens 

Feedback inhibition affected so ACTH rises and more cholesterol converted to androgens



Masculanization in girls; early development of masculine characteristics in boys; can have salt loss, causing dehydration



Treated with cortisol

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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g. Actions of steroid hormones 

Progesterone:

maintains

(with

estradiol)

uterine

endometrium

for

implantation; differentiation factor for mammary glands 

Estradiol -

Female: regulates gonadotropin secretion in ovarian cycle; maintains (with progesterone) uterine endometrium; differentiation of mammary gland



Male: negative feedback inhibitor of Leading cell synthesis of testosterone

Testosterone: converted to dihydrotestosterone by reduction in target tissues; production of sperm proteins in Sertoli cells and secondary sex characteristics (male)



Cortisol: stress adaptation through various cellular effects; slight elevation of liver glycogen; suppresses immune responses



Aldosterone: acts on kidney to cause sodium resorption into blood; raises blood pressure

K. VINOTH KALAISELVEN., Academia.edu/ Asst. Prof., Islamiah College, VNB.

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