• Cells in the raphe nuclei of brainstem convert L-tryptophan by tryptophan hydroxylase (TPH) to 5-hydoxytryptamine (5-HTP), and furtherly, by amino acid decarboxylase (DDC) to serotonin (5-HT). This is broken down by monoamineoxidase (MAO) to 5-HIAA. Serotonin is released into the synapse in a similar fashion to norepinephrine. Two presynaptic serotonin receptors serve as both brakes and enhancers of serotonin release when blocked by serotonin or norepinephrine, while the postsynaptic receptors regulate the release of the serotonin signal into the neuron. Serotonin producing neurons extend to the cerebellum, basal ganglia, frontal cortex, amygdala, thalamus, hypothalamus and limbic system, and down the spinal cord.  TPH1 is in several tissues, and TPH2, is a brain-specific isoform. Ovarian hormones can affect the expression of TPH (postpartum depression and premenstrual stress syndrome).
• Enterochromaffin cells in the gastrointestinal tract
• Platelets

Picture 1. Serotonin synthesis

Serotonin Effects

Serotonin effects include:

• Serotonin is found in the GI tract,… from mood to anxiety to sleep (serotonin makes melatonin, which regulates sleep) to sexual response to food craving and (in)digestion.
• Intestinal serotonin may inhibit bone formation (2)
• As a neurotransmitter: modulation of anger, aggression, body temperature, mood, sleep, human sexuality, appetite, and metabolism, as well as stimulating vomiting  (2).
• In platelets - post-injury vasoconstriction
• Nausea/vomiting (Dolasetron blocks serotonin so it helps in nausea)

What Affects Serotonin Release?

This:

• Serotonin transporter  facilitates re-uptake of serotonin into presynapses
• Exercise

Substances with Serotogenic Action:

Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake including (2):

• The empathogen MDMA (ecstasy) releases serotonin from synaptic vesicles of neurons.
• Amphetamine
• Cocaine
• Dextromethorphan (an antitussive)
• Tricyclic antidepressants (TCAs)
• Selective serotonin reuptake inhibitors (SSRIs) (2).
• The psychedelic drugs psilocin/psilocybin, DMT, mescaline, and LSDare agonists primarily at 5-HT_2A receptor.
• MAO inhibitors
• Tryptophan and5-hydroxytryptophan (5-HT) cross blood-brain barrier and are converted to serotonin
• Some cancers(carcinoid) secrete serotonin or 5-HIAA

Foods High in Serotonin

These include:

• Nuts of the walnut (Juglans) and hickory (Carya) genuses
• Plantain, pineapple, banana, kiwifruit, plums, and tomatoes.
• Fish, chicken and turkey
• Avocado
• Whole meal bread
• High-fibre cereals
• Tryptophan is found in bananas, pineapples, plums, turkey and milk

What is required to increase serotonin production is an increase in the ratio of tryptophan to phenylalanine and leucine. Fruits with a good ratio include dates, papaya and banana. Foods with a lower ratio inhibit the production of serotonin. These include whole wheat and rye bread.

Low Serotonin

• Problems with concentration and attention (1)
• Depression
• Chronic fatigue
• Nonrefreshed sleep; we can’t go to sleep at night as our mind/thought is racing ( “My mind won’t shut up!” ); early-morning awakening
• Loss of appetite and subsequent weight loss or a craving for sweets and carbohydrates when the brain is trying to make more Serotonin.
• Total loss of sexual and other interest is present. In fact, there is loss of interest in everything
• People whose serotonin levels have been artificially lowered will reject unfair offers 

References:

1. http://www.enotalone.com/article/4116.html
2. Serotonin inhibits bone formation http://en.wikipedia.org/wiki/Serotonin
3.  Exercise releases serotonin  (serendip.brynmawr.edu)

Testosterone:

• In puberty helps a boy in growth of the penis and testes, growth of facial and pubic hair, deepening of the voice, increase in muscle mass and strength, and increase in height.
• In adult man maintains sex drive, sperm production, male hair patterns, muscle mass, and bone mass
• Lowers blood sugar
• Increases bone mineral density in elderly men (1)

Testosterone Conversion

Testosterone converts to (5, page 24):

• Dihidrotestosterone (in testis, liver, brain, prostate, external genitalia)
• Androsterone
• Androstenedione
• Estradiol (in testis, liver, brain)
• Glucuronide
• Etiocholonolone

What Affects Steroid Production?

Below is the scheme of synthesis of steroid hormones (click image to enlarge it).

Substances and enzymes affecting steroidogenesis (5):

• Hydrogene peroxide (H2O2) (blocks conversion of pregnenolone to progesterone)
• Nitrous oxide  (NO) (blocks steroid production)
• StAR (Steroid Acute Regulator) gene codes StAR protein that transfer cholesterol into mitochondria. Growth hormone, estradiol, calcium, and IGF-1 upregulate StAR gene, thus enhancing steroid production.
• Enzyme P450SCC converts cholesterol into pregnenolone (in mitochondria)
• Enzyme 3ßHSD converts pregnenolone to progesterone, and DHEA to androstenedione (3ß-HSD is stimulated by FSH, via LH)
• 5? reductase converts testosterone to dihydrotestosterone (DHT)
• Aromatase converts testosterone to estradiol 
• Substances affecting steroidogenesis (5, pages 34-35)
• Dioxine (fatty meats, dairy) > low testosterone, and limited prostate growth
• Aminoglutethimide > low testosterone
• Lead, cadmium > low testosterone

What Affects Testosterone Blood Levels?

The following (1):

• Gonadotropin Releasing Hormone (GnRH) from hypothalamus stimulates secretion of LH
• LH  from pituitary gland stimulates secretion of testosteron from testes
• Testosterone suppresses the release of GnRH from the hypothalamus (negative feedback)
• Low testosterone production:
  • Chronic illness
  • Delayed puberty
  • Hypopituitarism
  • Prolactinoma
  • Testicular failure
• Steroid Hormone Binding Protein (SHGB) binds testosterone in blood. Increased SHGB lowers free testosterone in blood.
• Obesity – enzyme aromatase in fat tissue converts testosterone in estradiol thus lowering testosterone
• Zinc increases  testosterone level
• A bioflavonoid called chrysin (in honey) has shown potential as a natural aromatase inhibitor. The Life Extension Foundation has identified a novel supplement called piperine that increases the bioavailability of chrysin
• Carnitine
• Muira puama
• Quercetin in red wine inhibits aromatase thus elevating testosterone
• Antioxidants (vitamin A, and E, zinc, and selenium) all support testosterone production 

Low Testosterone (Androgen Deficiency)

Symptoms of low testosterone (2,3):

• Decreased sex drive (libido)
• Inadequate erections
• Increased breast size and tenderness
• Afternoon fatigue
• Symptoms similar to menopause in women (e.g., hot flashes, increased irritability, inability to concentrate, depression)
• SEVERE ANDROGENE DEFICIENCY:
• Loss of body hair
• Loss of muscle mass
• Fragile bones
• Smal and soft testes

Lab Results in Low Testosterone (4)

• Decreased bone density by dexa scan 
• Loss in height of more than 1 inch.
• High blood pressure and heart enlargement with associated chest pain
• Increase in abdominal girth with 40” as maximum for men and waist size of in excess of 34 inches in women
• Low Free Testosterone, occasionally low total testosterone, and low normal bioavailable testosterone
• Loss of penile reflexes and decreased penis sensitivity
• Lowered sperm count and fertility
• Insulin resistance
• High blood glucose
• Below normal HDL
• Low SHBG

References:

1. Testosterone increases bone density in elderly men  (lef.org)
2. Symptoms of low testosterone  (hormone.org)
3. Symptoms in severely lowered testosterone  (nlm.nih.gov/medlineplus)
4. Lab results in low testosterone  (wellnessmd.com)
5. Steroidogenesis of sex hormones  (epa.gov/endo)

• Increases Basal Metabolic Rate (BMR) > increased heat production 

Hypothyroidism

What Lowers TSH Release (1)

Pituitary (hypophysis) hormone TSH (thyroid stimulating hormone) stimulates thyroid to release thyroxine (T4) and triiodothyronine (T3). T4 and T3, when they reach a certain level, lower release of TSH by negative feedback loop. In low T4/T3 (hypothyroidism) TSH will be high, and in high T4/3 (hyperthyroidism) TSH will be low (1). Other factors that lower TSH level:

• Long term stress
• Prolonged cortisol excess
• Aging
• Infection
• Fever
• Trauma
• Caffeine
• Somatostatin
• Dopamine or L-dopa
• Adrenaline (sometimes)
• Amphetamine

Above factors may cause that TSH will be normal, despite hypothyroidism (2).

Symptoms of Hypothyroidism (3):

• Fatigue
• Insomnia
• Depression
• Anxiety and panic attacks
• Decreased memory
• Inability to concentrate
• Weight gain
• Fluid retention
• Puffy face, swollen eyelids
• Dull facial expression
• Swollen legs and feet, swollen hands, swollen abdomen
• Carpal tunnel syndrome
• Constipation
• Headaches
• Brittle nails
• Dry skin
• Elbow keratoses
• Yellowish discoloration of the skin
• White patches on the skin (vitiligo)
• Diffuse hair loss
• Coarse dry hair
• Menstrual irregularities
• Poor circulation
• Muscle and joint pain
• Morning stiffness
• Muscle cramps
• Reduced heart rate
• Low blood pressure
• Slow movements
• Decreased sexual interest
• Low body temperature
• Cold intolerance, cold hands and feet
• Husky voice
• Increased LDL

Thyroid Function and Cortisol

Cortisol controls thyroxine activation at the cell level. Often, symptoms of hypothyroidism are due to adrenal hormone imbalances. If a trial of thyroid hormone resulted in significant but temporary relief of symptoms of hypothyroidism, blood cortisol levels and rhythm should be checked (4).

References:

1. Thyroid function  (endocrineweb.com)
2. What lowers TSH release  (doctorsaredangerous.com)
3. Hypothyroidism symptoms  (worldhealth.net)
4. Cortisol influence on thyroxine activity  (nutrition4health.org)

• Low body temperature for at least one month, at least 0,5°C (0,9°F) lower than your usual temperature
• Low appetite
• Fatigue
• Weigh gain
• Skin Rash…

..then you might have:

1. Lowered thyroid function (Hashimoto’s thyroiditis)
2. Increased adrenal funcion (Cushing’s syndrome)