LIPID METABOLISM 4

The endocrine system has both negative and positive feedback loops.

The target hormone could send out its hormone.

  1. Corticotropin-releasing hormone (CRH)

    • the hypothalamus secretes CRH (protein)

    • CRH stimulates the ACTH to release which is another protein in the blood. (ADRENAL CORTEX) right above the kidney

    • corticotropin interacts with G-protein-coupled receptors

    • Stimulates cAMP production

    • Activates cholesterol esterase

    • Cholesterol esters have been cleaved = FFA + Cholesterol

    • cholesterol = cortisol

    • cortisol is released as a hormone and can have a negative effect on the Body

    • Cortisol increases blood sugar levels and blood pressure.

  2. Gonadotropin-relasing hormone (GnRH)

    • mainly in males

    • Hypothalamus secretes GnRH

    • GnRH stimulates pituitary FSH and LH release

    • LH stimulates Leydig cell Testosterone production

      • LH interacts with G-Protein coupled receptors

      • Increases cAMP to activate PKA

      • activates cholesterol-modifying enzymes

      • it can stimulate male characteristics (muscle, S hair, Larynx)

    • Females reproductive cycle

      • GnRH stimulates Pituitary E2 production

      • FSH stimulates ovarian (Oestradiol) E2 production

      • LH levels eventually stimulate ovulation

      • E2 secreted by Ovaries suppresses/induces secretion from the hypothalamus and Pituitary (NEGATIVE FEEDBACK)

    1. Progestogen e.g progesterone - prepares the uterus for implantation and supports pregnancy

    2. Androgens C19 e.g testosterone

    3. oestrogens C18e.g. oesdtradiol

    4. Glucocorticoids C21 e.g. Cortisol

    5. Mineralocorticoids C21 e.g. Aldosterone

clipping off carbons as you go down.

All binds intracellular receptors that regulate gene expression

Pregnenolone are modifying enzyme.

Cytochrome P450 Enzymes (CYP) catalyze two hydroxylations (OH)

Pregnenolone = Various steriod hormones

  • Via Hydroxylations (lyase glucocorticoid to Androgens)

STEROID HORMONES

oestradiol controls the genes for the development of female secondary sex characteristics.

Estrogen receptor - Has a zinc-based binding DNA as well. It Binds to specific ERE elements of the DNA.

structural change enables transcriptional regulator recruitment

they switch on genes and hopefully bring out the female characteristics.

TAMOXIFEN complex

anti-cancer growth that inhibits cell growth and binds to the pocket normally occupied by oestradiol.

Tamoxifen extends from this pocket.

Helix 12 is not packed as usual

Helix 12 blocks coactivator-binding

DISEASE

Cushing’s syndrome

cause: Cortisol overproduction/exposure

increases blood sugar, pressure, circulation, and stress

symptoms

  • Obesity, especially in the torso

  • high blood pressure (from sodium retention)

  • high blood sugar

  • skin bruises

ADDISON DISEASE

causes: Low aldosterone (and cortisol)

symptoms

  • weigh loss,

  • fatigue,

  • muscle weakness,

  • Dark patches of skin caused by increased levels of melanocyte

treatment: hormone treatment

ANDROGEN EXCESS

Causes: High Androgen ( a male hormone)

symptoms:

  • irregular periods

  • excess hair growth

  • weight gain

  • thinning hair or hair loss

CONGENITAL ADRENAL HYPERPLASIA (CAH’s Disease)

cause: glucocorticoid deficiency

mainly 21-Hydroxylase deficiency (CYP21A2 gene)

symptoms

  • increase androgen

  • an enlarged adrenal gland at birth

  • atypical genitalia (females with CAH’s)

Treatment

  • genital surgery

  • salt supplements

  • cortisol or Aldosterone HRT

treatment

control symptoms, hormone removal (extremely high levels)

MENOPAUSE

Cause: Decrease in Oestrogen (less than a tenth)

  • hypothalamus released from inhibitory influence

  • pituitary activity increases

  • increase in FSH and LH

symptoms :

menstruation ceases

unpleasant physical and emotional symptoms

Treatments

HRT reduces symptoms

decrease calcium loss from bones (later osteoporosis)

STEROID DRUGS

Agonists - Activate nuclear hormone receptor

Antagonists - Inhibit nuclear hormone receptors

Two major classes

  1. corticosteroids

  2. Anabolic steroids

Corticosteroids

  • Artificial version of adrenal gland hormones

  • reduces immune system activity

  • decrease inflammation

used to treat

  • Asthma

  • chronic obstructive pulmonary disease

  • hay fever, hives, and eczema

  • pain

Anabolic steroids

synthetic hormones that mimic testosterone

promote an increase in muscle size

treatment for :

  • hormone problem in men

  • delayed puberty

  • muscle loss

high dosage dangers

  • Acne, increased aggression, mood swings, and paranoia

  • in males, decreased libido decreases testicle size and lower sperm count

  • in females, increased libido, loss of breasts, facial hair growth, hair loss

High cholesterol, increased heart attack/strokes, liver and kidney problems