Table of contents :

Helper cytotype => prohormone =>
• glandular cell => hormone
• factor : any of several substances or activities that are necessary to produce a result, e.g., a coagulation factor. Often, use of the term “factor” indicates that the chemical nature of the substance or its mechanism of action is unknown, as in endocrinology, where “factors” are renamed as “hormones” when their chemical nature is determined.
• neuron => neurohormone
• uncharacterized hormone is termed factor
=> modifying cytotype
=> biological effect(s) on target cytotype(s) expressing hormone receptor(s)
Chemical structure :
• small peptides
• large proteins
• amino acid derivatives
• catecholamines
• iodothyronins
• steroids
• retinoids
Plasma concentration relates to :
• synthesis
• incretion, which in turn relates to
• circadian rhythms
• stress
Receptors : 10^3-4 per target cell
Feedbacks :
• negative feedback : R₀ down-regulation
• positive feedbacks : coagulation, ovulation, R₀ up-regulation, choleretic effect
• ultrashort loop feedback : autocrinia. E.g. :
• hypothalamic neurons
• lactotropic cells
• short loop feedback : hormone produced by hypophysis inhibits hypothalamic neurons
• long loop feedback : hormone produced by target organ inhibits hypothalamic neurons
[HR] = R₀ ^. [(K_a ^. [H]) / (K_a + I)]
Scatchard plot : [HR] / [H] vs. [H] is nonlinear when :
• R₁ and R₂ exist with K_a,R1 > K_{a, R2} but R_{0, 1} < R_{0, 2}
• negative cooperativity
Once internalized in clathrin-coated vesicles (CCV), R may be degraded or recycled.
Fractioned turnover ratio (K) = [metabolic clearance ratio] / [distribution volume] ~ 1 / t_1/2 ~ 1 / M_r ~ ([H] + [H-carrier]) / [H-carrier]
Only the quote unbound to carrier(s) can be eliminated by kidneys : the rest is catabolyzed by the liver or within target cell types.
[H] is measured with radioimmunoassays at rest or after challenging.
hormone incretion rate = ([H]_{venous plasma} - [H]_{arterial plasma}) ^. f_blood = CE_H = [H]_plasma ^. metabolic clearance_H = ([H]_urine ^. V_urine ^. metabolic clearance_H) / renal clearance_H. Sometimes there is circadian variability. The first part of the equation can be used to look for ectopic incretion.
Metabolism :
• energy metabolism
• fuel reserves of a healthy (70 kg) adult man :
• fats : 14 kg (125,000 kcal available for energy expenditures)
• protein
• skeletal muscles : 6 kg (24,000 kcal available for energy expenditures)
• other : 6 kg (24,000 kcal available for energy expenditures)
• glycogen
• muscle : 0.15 kg (600 kcal available for energy expenditures)
• liver : 0.075 kg (300 kcal available for energy expenditures)
• free glucose : 0.02 kg (80 kcal available for energy expenditures)
• respiratory quotient (RQ) = V_CO2 / V_O2 =Avogadro's principle=> n_CO2 / n_O2 =
• >1 (FFA synthesis)
• 1  (carbohydrate oxidation)
• 0.8 (protein oxidation)
• 0.7 (FFA oxidation)
On average RQ = 0.82 => 4.85 Kcal are produced for every L of O₂ consumed
• basal metabolic rate (BMR) / basal energy expenditure (BEE) = 4.85 Kcal/L_O2 ^. 371 L O₂/day = 1800 kcal/day = 1000 ^. S [(kcal ^. m²) / die] = 70 ^. m_{lean body}^0.75 [(kcal ^. kg^0.75) / day] (Kleiber's law from fractal geometry). It represents the minimum amount of energy required to keep your body functioning, including your heart beating, lungs breathing, and body temperature normal. BMR measurements are typically taken in a thermally neutral environment in a darkened room upon waking after 8 hours of sleep; 12 hours of fasting to ensure that the digestive system is inactive; and with the subject resting (not sleeping) in a supine or reclining position. Equations have been developed to estimate BMR when testing is not practical :
• Harris-Benedict formula, 1919 :
• for males : 13.7516 x weight(kg) + 500.33 x height(m) - 6.7550 x age(years) + 66.473
• for females : 9.5634 x weight(kg) + 184.96 x height(m) - 4.6756 x age(years) + 655.0955
• Harris-Benedict formula recalculated by Roza-Shizgal :
• for males : 13.707 x weight(kg) + 492.3 x height(m) - 6.673 x age(years) + 77.607
• for females : 9.740 x weight(kg) + 172.9 x height(m) - 4.737 x age(years) + 667.051
According to today's test standards the Harris-Benedict equation does not estimate BMR, but rather RMR. This is because the test subjects did not spend the night at the test facility. The test subjects used to create the Harris-Benedict equation did not include an adequate representation of obese people, nor of younger and older people. These omissions continue to become more significant as our population becomes older and heavier. While all equations for predicting energy expenditure only make estimates, the Harris-Benedict equation typically overestimates by 5% or more.
Approximate BMRs in adults :
• 50 kg : 1300 kcal/day
• 60 kg : 1450 kcal/day
• 70 kg : 1600 kcal/day
• 80 kg : 1750 kcal/day
• 90 kg : 1900 kcal/day
• 100 kg : 2050 kcal/day
• resting metabolic rate (RMR) / resting energy expenditure (REE) : measurements are typically taken under less restricted conditions than BMR, and do not require that the subject spend the night sleeping in the test facility prior to testing. Equations have been developed to estimate BMR when testing is not practical :
•  Mufflin equation :
• for men: 10 x weight(kg) + 625 x height(m) - 5 x age(years) + 5
• for women: 10 x weight(kg) + 625  x height(m) - 5 x age(years) - 161
• metabolic rate (MR) : BMR (60-75%) + physical activity (15-30%) + diet-induced thermogenesis (7-13%) = 2,700 Kcal/day. Every day we introduce 1 kg food, 1.5 kg H₂O and 15 kg air into our bodies
• sedentary males and females : BMR x 1,375
• active males and females : BMR x 1,55
The equations do not take into account your body composition (percent muscle vs. fat) and are therefore less accurate if you have a non-typical amount of muscle. This is because muscle burns more calories than fat.
• intermediate metabolism
• anabolism
• catabolism
• evacuative metabolism
Specific resources
• epiphysis / pineal gland (see also diseases of epiphysis)

Embryogenesis : epiphyseal arch : the embryonic structure in the roof of the third ventricle from which the pineal body develops.
2 forms of biomineralization
• mulberry-type hydroxyapatite crystals
• cubic, hexagonal, and cylindrical calcite crystals < 20 mm in length with sharp edges and very rough surfaces. The calcite microcrystals are probably responsible for the previously observed second harmonic generation in pineal tissue sections
It is believed that the presence of 2 different crystalline compounds in the pineal gland is biologically significant, suggesting 2 entirely different mechanisms of formation and biological functions. Studies directed toward the elucidation of the formation and functions, and possible nonthermal interaction with external electromagnetic fields are currently in progress^ref
Cell types :
• pinealocytes / chief cells / epithelioid cells produce
• melatonin

Secretion is :
• inhibited by
• stress
• awakening
• light (retina =retinosuprachiasmatic tract=> suprachiasmatic nucleus of hypothalamus => paraventricular nucleus => epithalamus)
• stimulated by
• rest
• sleeping
Biological effects via MLT₁ and MLT₂ :
• in adult amphibians it produces lightening of the dermal pigmentation by promoting aggregation of melanosomes
• in mammals it influences hormone production and in many species it regulates seasonal changes such as reproductive pattern and fur color
• in humans it is implicated in the regulation of sleep, mood, puberty, and ovarian cycles (inhibition of GnRH / LHRH incretion)
• adrenoglomerulotropin is a substance occurring in blood and CSF that is thought to be secreted by the brain or pineal gland and is reported to stimulate aldosterone secretion by the adrenal glands
• interstitial cells : cells with elongated nuclei and long cytoplasmic processes, found in the perivascular areas and between the cords of pinealocytes in the pineal body, and regarded by some to be glial elements
• hypothalamus : the ventral part of the diencephalon that forms the floor and part of the lateral wall of the third ventricle. Anatomically, it includes the
• preoptic area / area preoptica / preoptic region : several groups of cells in the median plane immediately below the rostral commissure of the telencephalon that are functionally related to the hypothalamus
• optic tract
• optic chiasm
• mammillary or mamillary bodies / corpora mamillares : either of the pair of small spherical masses situated close together in the interpeduncular space rostral to the posterior perforated substance in the posterior hypothalamic region, consisting of two main nuclei, lateral and medial, and smaller associated aggregations of gray matter. It forms a portion of the limbic system
• tuber cinereum / tuberculum cinereum / gray tubercle : a layer of gray matter which is part of the hypothalamus; forming a part of the floor of the third ventricle, it lies in front of and between the corpora mammillaria and merges anteriorly into the infundibulum
• infundibulum
• neurohypophysis (considered a distinct structure for physiological purposes)
The hypothalamus may be divided into 5 regions or areas
• area hypothalamica rostralis / anterior hypothalamic area / preoptic area or region / regio hypothalamica anterior / anterior hypothalamic region : the most anterior part of the hypothalamus, lying adjacent to the lamina terminalis and superior to the optic chiasm, and comprising the lateral and medial preoptic nuclei, the supraoptic and paraventricular nuclei; and the anterior hypothalamic nucleus
• area hypothalamica dorsalis / dorsal hypothalamic area / regio hypothalamica dorsalis / dorsal hypothalamic region : the most dorsal part of the hypothalamus, comprising the entopeduncular nucleus and the nucleus of the ansa lenticularis
• area hypothalamica intermedia / intermediate hypothalamic area / regio hypothalamica intermedia / intermediate hypothalamic region : the part of the hypothalamus comprising the lateral hypothalamic region and the following nuclei: arcuate, tuberal, ventromedial hypothalamic, dorsomedial hypothalamic, dorsal hypothalamic, posterior periventricular, and infundibular
• area hypothalamica lateralis / lateral hypothalamic area / regio hypothalamica lateralis and lateral hypothalamic region : a part of the intermediate hypothalamic area lateral to the fornix and the mammillothalamic fasciculus
• area hypothalamica posterior / posterior hypothalamic area / regio hypothalamica posterior / posterior hypothalamic region : the most posterior part of the hypothalamus, consisting of the lateral and medial nuclei of the mammillary body and the posterior hypothalamic nucleus
... or into 3 longitudinal zones :
• periventricular zone
• medial zone
• lateral zone
The hypothalamic nuclei constitute that part of the corticodiencephalic mechanism that activates, controls and integrates the peripheral autonomic mechanisms, endocrine activity, and many somatic functions, e.g., a general regulation of water balance, body temperature, sleep, and food intake, and the development of secondary sex characteristics.
• supraoptic and paraventricular nuclei secrete vasopressin (VP) / antidiuretic hormone (ADH) and oxytocin (from neurohypophysis), which are stored in the pituitary
• arcuate and periventricular nuclei secrete many hypophysiotropic hormones in a pulsatile manner, by means of which it exerts control over functions of the adenohypophysis :
• releasing factors / releasing hormones are termed -crinins or -liberins
• inhibiting factors / inhibiting hormones are termed -statins
• CRH-increting neuron. Secretion is :
• stimulated by :
• noradrenaline
• serotonin
• acetylcholine
• GABA
Biological effects via CRHR₁ and CRHR₂ :
• induction of ACTH secretion in corticotropic cells of adenohypophysis
• a maternal mouse will attack any intruder to her nest if she thinks her pups are in danger. This apparently selfless response may be due to low levels of CRH. High levels of CRH in the brain are linked to fear and anxiety. So without it, a mouse is more likely to leap towards an intruder without a thought for herself. Perhaps lactation stimulates the brain to produce less CRH. Or maybe the brain's cells simply become less responsive to the hormone. Human postnatal depression is often linked to high levels of stress hormones. Some 10-15% of new mothers experience depression lasting > 2 weeks after giving birth, and around 50% of these require treatment with existing antidepressant medications. The fact that many depressed new mothers seem not to care about their baby's wellbeing could be because their raised levels of stress hormones prevent the low levels of CRH that seem to be required for the care of offspring.
• GnRH / LHRH-increting neuron. Secretion is :
• inhibited by ...
• dopamine
• melatonin
• b-endorphin
• stimulated by ...
• noradrenaline
GnRH neurons receive pheromone signals from both odor and pheromone relays in the brain and may also receive common odor signals. Moreover, feedback loops are evident whereby GnRH neurons could influence both odor and pheromone processing. Remarkably, 800 GnRH neurons communicate with 50,000 neurons in 53 functionally diverse brain areas, with some connections exhibiting sexual dimorphism^ref. Injection of conditional pseudorabies virus into the brain of an LHRH::CRE mouse line led to the identification of neuronal networks connected to LHRH neurons. Remarkably, and in contrast to established notions on the nature of LHRH neuronal inputs, major olfactory projection pathways were identified originating from a discrete population of olfactory sensory neurons but fail to document any synaptic connectivity with the vomeronasal system. Accordingly, chemosensory modulation of LHRH neuronal activity and mating behavior are dramatically impaired in absence of olfactory function, while they appear unaffected in mouse mutants lacking vomeronasal signaling. Further visualization of afferents to LHRH neurons across the brain offers a unique opportunity to uncover complex polysynaptic circuits modulating reproduction and fertility^ref.
t_1/2 = 4' (degraded by both hypothalamic and pituitary peptidases) : small quantities are found in the peripheral blood of nonpregnant females during the menstrual cycle. Pulsatile incretion (every hour) :
• higher frequencies cause initial gonadotropin increase for 4 hours, then a decrease termed pituitary densensitization (medical castration) via down-regulation of pituitary GnRH-R
• lower frequencies cause increase of FSH concentration due to slower metabolic clearance than LH
Biological effects via GnRH-R : induction of FSH and LH secretion in gonadotropic cells of adenohypophysis
• GHRH-increting neuron. Secretion is :
• stimulated by
• high protein diet
• fasting
Biological effects via GRP39 and GRP38 / MTLR1: induction of GH incretion in somatotropic cells of adenohypophysis
• TRH-increting neuron. Secretion is :
• stimulated by :
• estrogens
• serotonin
• histamine
• low temperature
• feeding
• inhibited by :
• glucocorticoids
• GABA
• DA
• adrenalin
• ACh
Normal plasma concentration : 25-100 pg/mL
Biological effects via TRH-R : induction of PRL incretion in lactotropic cells and of TSH incretion in thyrotropic cells of adenohypophysis
Secretions are regulated by neurons using as neurotransmitters
• dopamine
• acetylcholine
• GABA
• b-endorphin
• PACAP
Vascularization : hypophysiotrophic factors are released into superior hypophysary plexus, while hypophysary hormones are relased into lower hypophysary plexus. A third capillary plexus joins the 2 abovementioned plexuses and vascularize anterior pituitary gland (rete mirabile venosa)
• hypophysis (cerebri) / pituitary gland is located outside of the blood-brain barrier (BBB)
• anterior hypophysis / adenohypophysis / anterior pituitary / anterior lobe of hypophysis / lobus anterior hypophyseos / lobus glandularis hypophyseos (see also diseases of adenohypophysis) : it  has its origin in the Rathke pouch of buccal epithelium of the embryo and comprises
• pars tuberalis (near tuber cinereum of hypothalamus)
• pars distalis, the main body of the adenohypophysis. Its hormones are said -tropins when they target other endocrine glands.

Cell types :
• somatotrope or somatotroph or somatotropic cell / somatotroph increte growth hormone (GH) : secretion has zenit at 8 a.m. and nadir at 6 p.m.. Tissue-specific transcription factors : PROP-1, PIT1. Onset at fetal week 8. It is :
• stimulated by GH secretagogues (GHS) :
• hormonal stimuli
• GHRH
• ghrelin
• estrogens
• T₃
• cortisol
• glucagon
• vasopressin / ADH
• insulin
• prostaglandins
• metabolic stimuli
• L-Arg
• L-Lys
• L-Leu
• starvation
• hypoglycemia
• uremia
• ectopic CRF production
• inhibited by
• hormonal stimuli
• IGF-1
• SST / somatotropin release inhibiting factor (SRIF)
• metabolic stimuli
• hyperglycemia
• free fatty acids
• obesity
Secretion rate : 0.5-2 mg/die. Carrier proteins :
• albumin
• high affinity growth hormone binding protein (GHBP) is the soluble ectodomain of GHR (in other species it is a splice variant of the Ghr gene) generated by TNF-alpha converting enzyme (TACE) / ADAM17 and possibly related enzymes
t_1/2 = 20-25' .
Normal plasma concentration :
• fetus : 150 ng/mL
• birth : 40 ng/mL
• babies > 10 ng/mL or > 465 pmol/L
• adult : 1-5 ng/mL (100 pM)

	after physical effort	after Glc challenge
males	< 5 ng/mL or < 233 pmol/L	< 5 ng/mL or < 233 pmol/L
females	< 30 ng/mL or < 1395 pmol/L

Biological effects : the response to GH incretion is biphasic
• first indirect (IGF-1-dependent) insulin-like effects via IGF-1R / CD221 (also IGF-2-dependent effects via IGF-2R in embryo):
• stimulation of amino acids transport into cells
• stimulation of protein synthesis if amino acid are introduced with diet
• stimulation of increased muscle mass
• stimulation of bone growth
• stimulation of epiphysary cartilage growth acting on chondrocytes (they also have autocrine IGF-1 incretion)
• stimulation of nucleic acid synthesis and cell proliferation
Plasma carriers for IGFs :
• IGF-binding protein (IGFBP1)
• IGFBP2
• IGFBP3 (major carrying protein)
• IGFBP4
• IGFBP5
• IGFBP6
• IGFBP7
• IGFBP8 / connective tissue growth factor (CTGF)
• IGFBP9 / nephroblastoma overexpressed gene (NOV)
• IGFBP10 / cysteine-rich, angiogenic inducer, 61 (CYR61)
Normal IGF-1 plasma concentration :
• month 2 - age 5 : 17-250 ng/mL
• age 6-12 : 88-770 ng/mL = 0.08-2.8 U/mL
• age 13-15 : 200-1100 ng/mL
• age 16-24 : 180-780 ng/mL = 0.9-5.9 U/mL
• age 25-50 : 90-490 ng/mL
• adult male : 0.34-1.9 U/mL
• adult female : 0.45-2.2 U/mL
• age > 50 : 71-290 ng/mL
• then direct (IGF-1-independent) anti-insulin effects via GHR (glucagon-like effects, but systemic, hence adrenalin-like, important during first days of starvation) :
• diabetic ketoacidosis
• hyperglycemia
• insulin resistance => hyperinsulinism
• gluconeogenesis
• ketogenesis
• lipolysis
• stimulation of protein synthesis if amino acid are introduced with diet
• Na⁺ / H₂O retention
• stimulation of epiphysary cartilage growth acting on chondroblasts
• gonadotrope, gonadotroph or gonadotropic cells / gonadotroph (basophilic cells). Tissue-specific transcription factors : SF-1, DAX-1. Onset at fetal week 12.
• follicle-stimulating hormone (FSH)-increting cell.

Secretion is monophasic and
• stimulated by :
• GnRH / LHRH
• activin A (inhibited by follistatin)
• activin AB (inhibited by follistatin)
• inhibited by :
• inhibin
Secretion rate : 200 IU/day. Pulsations are slower than for LH : they occur every 1-2 hours in follicular phase and every 4 hours in luteal phase. t_1/2 = 180'.
Normal plasma concentration :
• males
• prepuberal males : < 3 mIU/mL
• adult males : 3-18 mIU/mL
• females
• prepuberal females : 0.8-7.2 mIU/mL
• adult females
• follicular stage : 2.9-10.2 mIU/mL
• half-cycle peak = 13-41 mIU/mL
• periovulatory stage : 4.4-22.4 mIU/mL
• luteinic stage : 1.3-7.1 mIU/mL
• postmenopause : 30-170 mIU/mL
Biological effects via FSH-R (up-regulated by estradiol / E₂) :
• induces granulosa cells to up-regulate aromatase / CYP19 expression (hence promoting conversion of testosterone into 17b-stradiol / E₂), and then LH / hCG-R (accompanied to down-regulation of FSH-R); also induces secretion of follicular fluid
• induces Sertoli cells to increte AMH
• luteinizing hormone (LH)-increting cell

Secretion is biphasic and stimulated by GnRH / LHRH and high dose estradiol / E₂. With onset of puberty LH concentratios become higher than FSH and pulsatile increation pattern of LH occurs even during daytime (no longer only during sleep)
Secretion rate : 1,000 IU/day. t_1/2 = 30'.
Normal plasma concentration :
• males :
• prepuberal males : < 1.7 mIU/mL
• adult males : 3-18 mIU/mL
• females
• prepuberal females : < 2.5 mIU/mL
• adult females
• follicular stage : 0.9-9.7 mIU/mL
• periovulatory stage : 5-57 mIU/mL
• pre- and postovulatory stage : 2.4-34.5 mIU/mL
• half-cycle peak : 43-187 mIU/mL
• luteinic stage : 0.6-9 mIU/mL
• postmenopause : 30-150 mIU/mL
Biological effects via LH / hCG-R :
• induces Leydig cells to produce testosterone
• induces granulosa cells and inner techa cells to produce testosterone and progesterone
• lactotrope or lactotroph or lactotropic cell / lactotroph increte prolactin (PRL) / lactotropin : secretion has zenit at 12 p.m. and nadir at 8 a.m. Tissue-specific transcription factors : PROP1, PIT1. Onset at fetal week 12. It is
• stimulated by :
• TRH (increase >> 100%)
• VIP
• estradiol / E₂
• suction of nipple of lactating breast
• sleep
• stress
• physical exercise
• inhibited by :
• DA
• SST
Both a reserve pool and a release pool exist.
Secretion rate : 50-200 IU/day. t_1/2 = 20-80'.
Normal plasma concentration : 2-15 ng/mL = 0.08-6 nmol/L
• prepuberal males : 25-350 mIU/L (1-20 ng/mL)
• adult males : 71-330 mIU/L
• prepuberal females : 88-590 mIU/L
• follicular stage : 93-467 mIU/L
• periovulatory stage : 145-261 mIU/L (5-25 ng/mL)
• luteinic stage : 106-551 mIU/L
• menopause : 69-360 mIU/L
Biological effects via PRLR : hypertrophy of mammary gland
• corticotrope cell / corticotrophlipotroph cell / corticotroph increte adrenocorticotropic hormone (ACTH) / corticotropin. Tissue-specific transcription factors : PTX-1, CUTE. Onset at fetal week 6. Secretion is :
• stimulated by
• stress and physical exercise
• insulin-induced hypoglycemia
• CRH
• vasopressin / ADH via V_{1b / 3}
• serotonin
• histamine
• acetylcholine
• inhibited by
• GABA
• cortisol
t_1/2 = 10-25'. Normal plasma concentration at 6 a.m. : 15-70 pg/mL (3.3-15.4 pmol/L)
Incretion rate : 25 mg/die.
Biological effects via MC2R / ACTHR :
• induction of cortisol secretion by zona reticularis, fasciculata, and glomerularis of adrenal cortex
• induction of lipolysis
• thyrotrope or thyrotroph or thyrotropic cell / thyrotroph secrete TSH / thyrotropin : secretion has zenit at 12 p.m. and nadir at 8 a.m. Tissue-specific transcription factors : PROP-1, PIT-1. Onset at fetal week 12. It is :
• stimulated by :
• TRH (15' after exogenous administration)
• estradiol / E₂
• prostaglandins
• inhibited by :
• DA
• 3,5,3'-triiodothyronine (L-T₃)
• SST
• cholecystokinin (CCK)
• gastrin
• serotonin
• cortisol
• testosterone
• neurotensin (induced by vasopressin / ADH)
Normal plasma concentration : 0.5-5.0 mU/mL. t_1/2  = 50' => very few fluctuations despite pulsating secretion.
Biological effects via TSH-R : induction of thyroid hormones incretion
• chromophobe cells / chromophobic cells / C cells / chief cells / g cells of hypophysis : small, faintly staining cells with scanty cytoplasm found often in clusters in the center of the cell cords in the adenohypophysis; their cytoplasm was formerly thought to be nongranular, but the granules are now known to be simply small and sparse. These cells are increased in chromophobic or null-cell adenomas
• pregnancy cell : an altered chromophobe cell found in the adenohypophysis in pregnant women
• S cells : mucoid cells of the adenohypophysis that contain a cysteine-rich protein
• pars intermedia  / intermediate hypophysis (sometimes considered to be part of the neurohypophysis; see also diseases of intermediate hypophysis)

Cell types :
• b-endorphin

Biological effects via  :
• inhibition of CRH incretion
• inhibition of GnRH / LHRH incretion
• inhibition of oxytocin (OT) incretion
• a-MSH- and g-MSH-increting cell. Secretion is :
• stimulated by :
• ADH
Biological effects via MC1R => ... => CREB => MITF => tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein 2 (TRP2) / dopachrome tautomerase (DCT) => increased melanin synthesis in melanocytes
• b-LPH- and g-LPH-increting cell

Biological effects via MC1R :
• pharyngeal hypophysis / pars pharyngea lobi anterioris hypophyseos / pharyngeal pituitary / hypophysis pharyngealis : a small median residual collection of adenohypophysial glandular tissue in the mucoperiosteum of the roof of the nasopharynx; it develops from Rathke's pouch in the embryo
• posterior hypophysis / neurohypophysis / posterior pituitary / posterior lobe of hypophysis or of pituitary gland / lobus posterior hypophysis (see also diseases of neurohypophysis) : the posterior lobe of the hypophysis (pituitary gland), the neural portion of the gland. It consists of
• neural stalk
• infundibulum which is continuous with the supraoptic and paraventricular nuclei in hypothalamus
• median eminence
• neural lobe : the main body of the neurohypophysis
It originates in the embryo as an evagination from the floor of the diencephalon.
Cell types : hormone-containing granules are seen at TEM as Herring bodies.

• oxytocin (OT)- and neurophysin I-increting cell

Biological effects via OT receptor
• induction of labor
• post-partum hemostasis
• lactation
Inactivated by OTase / oxytocinase / leucyl/cystinyl aminopeptidase (LNPEP)
• arginine vasopressine (VP) / antidiuretic hormone (ADH)- and neurophysin II-increting neurons are parvicellular neurons of paraventricular nucleus

Secretion is
• stimulated by :
• plasma hyperosmolarity (osmoceptors)
• hypovolemia => systemic arterial hypotension (baroceptors, far less sensitive)
• nausea and vomiting
• pain
• stress
• pregnancy
• hypoglycemia
• hypoxia
• drugs :
• morphine
• nicotine
• cyclophosphamide
• inhibited by
• plasma hypoosmolarity
• hypervolemia => systemic arterial hypertension
• drugs :
• ethanol
• clonidine
• haloperidol
Biological effects : induces expression of vasopressin-induced transcript (VIP32) and activates cullin 5 (CUL5) / vasopressin-activated calcium-mobilizing receptor-1 (VACM1)
• V_1a : ejaculation and arteriolar vasoconstriction
• V_1b / V₃ : stimulation of ACTH incretion
• V₂ : increased H₂O reabsorption from distal convoluted renal tubule and collecting duct via up-regulation of aquaporin 2 translocation into apical membrane of principal cells
Inactivated by OTase / oxytocinase / leucyl/cystinyl aminopeptidase (LNPEP)
The hypophysis root consists of pars tuberalis adenohypophysis and neural stalk.
• thyroid / glandula thyroidea (see also diseases of thyroid) : an endocrine gland normally situated in the lower part of the front of the neck, consisting of 2 lobes, one on either side of the trachea and joined in front by a narrow isthmus

Ontogenesis : at week 3 of pregnancy the gland on the floor of embryonary pharynx at the level of foramen caecum in the posterior part of the tongue invaginates into the Bochdalek, His or Vater thyroglossal or thyrolingual duct / ductus thyroglossalis; in 75% of people the distal part of the duct differentiates to form the pyramidal lobe the thyroid and the remainder becomes obliterated, but occasionally persists into adult life, giving rise to cysts, fistulas, or sinuses or small salivary glands in the last part
Lobes :
• left lobe
• right lobe (usually larger than left one)
• Morgagni-Lalouette's pyramidal lobe of thyroid gland / lobus pyramidalis glandulae thyroideae : an occasional third lobe (found in 15-80% of people) that extends upward from the isthmus of the gland across the thyroid cartilage to the hyoid bone; it is the residuum of the thyroid stalk of the fetus
Vascularization :
• upper thyroideal artery
• lower thyroideal artery
• Neubauer's artery
TFs essential for thyroid development : thyroid transcription factor 1 (TTF-1) / NKX2A, FOXE1 / TTF-2 / FKHL15, and PAX8
Cell types :
• follicular epithelial cells of the thyroid / thyrocyte form follicles 30 mm in diameter and secrete :
• thyroglobulin is a p330 monomer containing 134 Tyr residues : only 30-40 are iodated, but steric hindrance allows only 8-10 pairings, so that only 4 or 5 iodothyronin molecules are formed per thyroglobulin molecule. TG is arranged into 19S dimers or 27S tetramers. Thyroid peroxidase (TPo) catalyzes :
• the iodination of tyrosine residues to 3- or 5-monoiodothyronin (MIT) or 3,5-diiodothyronin (DIT) in thyroglobulin (iodine enters thyrocytes via NIS ; see also iodine metabolism)
• phenoxy-ester formation between pairs of iodinated tyrosines to generate
• the thyroid hormones
• 3,5,3'-triiodothyronine (L-T₃) (10%; 6.4 mg/die; 20% of total L-T₃)
• 3,5,3',5'-tetraiodothyronine / thyroxine (L-T₄) (80%; 90 mg/die)
• inactive hormone 3,3',5'-triiodothyronine (reverse T₃ / L-rT₃) (< 1%)
Secretion is :
• stimulated by :
• prostaglandins
• estradiol / E₂
• VIP
• gastrin-releasing peptide (GRP)
• helodermin-like peptide
• inhibited by :
• acetylcholine
• neuropeptide Y (NPY)
• noradrenaline
• somatostatin (SST)
• calcitonin
• katacalcin
• calcitonin gene-related peptide (CGRP)
• endothelin
• atrial natriuretic peptide (ANP)
• growth factors
• IGF-1
• EGF
• cytokines
• TGF-b
The prohormone L-T₄ is peripherally converted to bioactive 3,3',5-L-T₃ (25.6 mg/die; 80% of total L-T₃) via 5'-deiodination / outer ring deiodination (ORD) catalysed by :
• deiodinase 1 (D₁) (liver, kidney, thyroid; low affinity for L-T₄ ). It also degrades both L-T₄ and 3,3',5-L-T₃ by inner ring deiodination (IRD).
• deiodinase 2 (D₂) (brain, pituitary, brown adipose tissue, heart, skeletal muscle, and thyroid; high affinity for L-T₄)
20% of L-T₄ and 70% of 3,3',5-L-T₃ are located intracellulary.
Deiodinase 3 (D₃) (placenta, several fetal tissues, skin, brain) > deiodinase 2 (D₂) catalyzes the 5-deiodination (IRD) of
• L-T₄ to 3,3',5'-triiodothyronine (reverse T₃)
• 3,3',5-L-T₃ to 3,3'-T₂ (inactive metabolite)
All iodinated catabolytes are sulfated and glucunated in hepatocytes.

	t1/2	plasma concentration	plasma molarity
TT4	7 days	4-12 mg/dL	52-154 nM
FT4		0.7-2.3 ng/dL (0.02%)	9-20 pM
TT3	0.75 day	75-195 ng/dL	1.16-3 nM
FT3		0.25-0.58 ng/dL (0.3%)	4-8 pM
T3 resin captation		25-25%
TrT3	0.8 days	0.04 mg/dL
FrT3		13-53 ng/mL	0.2-0.8 nM
thyroxin-binding globulin (TBG) / SERPINA7 (it binds 67% of BT4 and 1% of BT3)		2 mg/dL
TBG-binding capacity		15-24 mg T4/dL	193-322 nM
transthyretin / thyroxin-binding prealbumin (TBPA)	< 2 days	15 mg/dL
albumin	20 hours	3.5-5.2 g/dL
thyroglobulin (TG)		3-30 ng/mL

thyroid function test : any of various diagnostic procedures measuring the functioning of the thyroid gland
• protein-bound iodine test (no longer used) : the amount of iodine firmly bound to protein in the serum was determined by precipitating the proteins, yielding an estimate of serum thyroid hormone concentration. Errors were introduced if iodine compounds from nonthyroid sources were present
• perchlorate discharge test : 1-2 hours after administration of radioiodine, perchlorate is administered to block further iodine uptake and flush from the thyroid gland any that has not bound to thyroid proteins. In euthyroid patients only trace amounts will be flushed out; the discharge of significant amounts indicates a defect in thyroid iodine binding.
• thyroid-stimulating hormone (TSH) stimulation test : a thyroid function test in which thyrotropin (TSH) is administered intramuscularly and the thyroid gland is monitored over time with scintiscanning or radioimmunoassays for a response or areas of decreased responsiveness. The test was formerly also much used for determining whether hypothyroidism was caused by thyroid gland failure or by deficiency in thyrotropin
• thyrotropin-releasing hormone (TRH) stimulation test (for pituitary release of thyrotropin): a bolus of TRH is administered and serum concentrations of thyrotropin are assessed at intervals; if serum levels do not increase within 30 to 40 minutes, the pituitary thyrotrophs are dysfunctional
• thyroid suppression test : after administration of liothyronine for several days, radioactive iodine uptake is decreased in normal persons but not in those with hyperthyroidism
• radioactive iodine uptake test : a known quantity of radioiodine is administered and 24 hours later the per cent is calculated that has been absorbed by the thyroid gland. Patients who have recently been exposed to iodine compounds, such as in dietary supplements, contrast media, medications, or antiseptics, may not be good candidates for this test
• triiodothyronine resin uptake test : measuring how many sites on TBG are occupied by endogenous T₃ and how many sites remain available. An excess of radioactive exogenous triiodothyronine is added to the sample, followed by the addition of a resin that also binds T₃. A portion of the radioactive T₃ binds to sites on TBG not already occupied by endogenous thyroid hormones, and the remainder binds to the resin. The amount of labeled hormones bound to the resin (the triiodothyronine resin uptake) can be subtracted from the total that was added and the remainder is the amount that bound to the unoccupied binding sites on the thyroxine-binding globulin.
• thyroid hormone binding ratio (THBR) at T₃ resin uptake text
• FT₃ index = THBR ^. FT₃  : an estimate of the physiologically active free triiodothyronine in serum
• FT₄ index = THBR ^. FT₄  : an estimate of the physiologically active free thyroxine in serum
Only T₃ binds TRs, ubiquitously expressed (pantropic hormone)
Biological effects of 3-iodothyronamine (T₁AM) via trace amine receptor 1 (TAR1) : profound hypothermia and bradycardiawithin minutes^ref
Biological effects of F3,5,3'-triiodothyronine (L-T₃) via T3Ra and T3Rb, the effects of which manifest over hours and days :
• differentiation of most organs (CNS, exocrine pancreas, liver, heart ventricles, skull, lungs, gametogenesis)
• increases in metabolic rate : proteolysis
• positive inotropic effect (up-regulation of b₁-AR)
• tachycardia
• hyperglycemia due to
• insulin resistance
• increased intestinal glucose absorption
• glycogenolysis
• gluconeogenesis
=> diabetic ketoacidosis
• hyperthermia :
• up-regulation of uncoupling proteins (UCP) in mitochondria
• lipogenesis => lipolysis => ketogenesis
• awakening
• calcitonin