A clinical approach to somatotropic axis

Chapter 6

A clinical approach to somatotropic axis Introduction The somatotropic axis is the second of two anabolic axes. It is the great fashioner of structure. It lengthens, widens, expands, and ultimately helps replicate the number of structural units. In function, it is the great furnisher of regular, steady energy for acute and chronic needs, both during and outside adaptation. It stands at the crossroad of endocrine function. It is the end of the first, turns it to the second loop, and then completes the second loop. In summary, the somatotropic axis plays a key role in the sequencing of catabolic and anabolic activity, first loop preparation, and second loop completion. The somatotropic axis has four unique features related to all these activities. First, prolactin (PL), a pituitary somatotropic hormone, has a thyrotropic hypothalamic hormone that stimulates it (TRH). It is the only hormone whose axial hypothalamic counterpart (somatostatin) inhibits it. In all other cases, hypothalamic hormones stimulate pituitary counterparts. Second, the somatotropic axis has three hypothalamic and two pituitary hormones, paired as such: GHRH (growth hormone-releasing hormone) stimulates GH (growth hormone), TRH (thyrotropin releasing hormone) stimulates PL (prolactin), somatostatin inhibits prolactin. Recall that the other anabolic axis, gonadotropic, has two pituitary but one hypothalamic hormone. In peripheral gonadotropic activity, progesterone serves as the competitive agonist-antagonist factor in regulating estrogens and androgens in both timing and duration of activity. In the somatotropic axis, PL stimulates insulin from the endocrine pancreas. Third, instead of a peripheral hormone antagonizing insulin, it is an intracellular effect stimulated by GH, namely insulin resistance, which maintains the competitive agonist-antagonist actions. Finally, rather than having two or three peripheral hormones, the somatotropic axis has the greatest number of peripheral hormones ranging from cellular growth factors (i.e., insulin, insulin like growth hormone, etc.) to regulators of digestion and nutrient extraction (i.e., vasoactive intestinal peptide, cholecystokinin, etc.). The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00006-7 © 2019 Elsevier Inc. All rights reserved.

A brief review of somatotropic endocrine function The somatotropic axis manages nutrients, cell structure, cell energy, storage of energetic material, and progression of endocrine loops. ●

● ● ●

●

Nutrients: Extraction and processing: exogenous and endogenous sources, availability, distribution, timing of entry of nutrients Architecture: Growth factors Energy: Glucose and lipids for ATP production Storage: Carbohydrates as glycogen, lipids as adipocytes Loops: Starter energy before first loop, passage from first to second loop, completion of second loop

Somatostatin has central and peripheral actions. Its general function is as an inhibitor of anabolic hormones that ultimately is pro-anabolic. The true managers of peripheral somatotropic activity are the pituitary hormones: growth hormone (GH) and prolactin (PL). They have agonistantagonist function that is competitive and additive in nature. The chronologic relationship of GH and Prolactin is key to the regulation of both somatotropic function and endocrine progression throughout the two loops. GH activity is summarized in Table 6.1, Prolactin in Table 6.2. The peripheral hormones adapt the organism in its basal, immediate, and chronic demands. Insulin-like growth factor manages growth, adhesion, and expansion of cells. It serves as a barometer of nutritional integrity and somatotropic synchronization (Table 6.3). Glucagon participates in basal and adaptation states: it provides substrates for structural and functional energy (glucose, free fatty acids). It is a catabolic hormone in an anabolic axis, produced in Islet cells of the endocrine pancreas. It constantly functions to regulate glycemia, and the availability of both glucose and free fatty acids for cellular oxidation and ATP production (Table 6.4). Glucagon has an agonist-antagonist, competitive-additive relationship with insulin, similar to the relationship between growth hormone and prolactin. 123

124  The theory of endobiogeny

TABLE 6.1  Summary of growth hormone action by location and endobiogenic mechanism Location

Mechanism

Action

Comment

Central

Endocrinometabolic

Dreams

GHRH initiates, TRH affects vivacity of dreams

Peripheral

Endocrine (liver)

IGF production

IGF’s responsible for most effects attributed to GH on bone, muscle and cartilage

Endocrinometabolic (nonvital organs)

Insulin resistance

Ensures timing and productivity of GH as a distributor of nutrients by delaying time of glucose entry into cell

Endocrinometabolic (liver)

Glucose: gluconeogenesis, blocks hepatic uptake of glucose

Favors circulating glucose for second loop entry and completion of anabolism

Nutrient distribution

Lipids: lipolysis

Augments free fatty acids for nonglucose ATP production in first loop

Amino acids: uptake into cells

Prepares cells to produce enzymes, DNA when the cell enters a construction phase

Electrolytes: calcium, phosphorous, sodium

Calibrates quantitative entry from effects of catabolic cortico- and thyrotropic activity

Endocrinotissular

General plan of growth and shaping of all organs

Vertical growth of muscle, bone, cartilage, special tropism for liver and endocrine pancreatic integrity

Metabolic

Restoration, reparation of cellular elements

All classes and structures: glycolipids, proteoglycans, cell membrane, DNA integrity, etc.

GHRH, growth hormone releasing hormone; IGF, insulin like growth factors; TRH, thyrotropic releasing factor.

TABLE 6.2  Actions of prolactin by location Location

Action

Comment

Hypothalamus

CRH relaunching

Relaunches ACTH, re-adapts cortisol

Pancreas, endocrine

Insulin excretion

Helps close anabolic loop

General

Wide of structure

Suppresses apoptosis, increases proliferation of cells; when activity estrogens + progesterone, favors proliferation of cancer cells in breast, ovaries, uterus

Immunity: auto-defender of life

Inflammation, extravasation

Favors pus production

Vasculature: auto-sustainer of life

Angioneogenesis

Favors metastasis of tumors, especially breast and prostate

Mammary glands: allosustainer of life

Lactation: production and flow

Oxytocin stimulates let-down

TABLE 6.3  Actions and effects of insulin-like growth factor Action

Effect

Comment

Endocrinometabolic

Inhibits apoptosis Promotes oxidation

Oxidation favors increased ATP production, free radical production

Endocrinotissular

Lengthening of tissues and organs

Most targeted: bone, cartilage, muscle

Nutritional integrity

IGF-1 expression commensurate to mineral intake

Most beneficial: zinc, selenium, and magnesium

Longevity

Inversely correlated to IGF-1

Reduce caloric intake by 15%

Pathophysiology

Insufficient IGF-1

Failure to thrive in children

Excess IGF-1

Atherosclerosis, uterine fibroids, and tumors

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TABLE 6.4  Actions of glucagon in management of glucose and lipids Metabolite

Action

Comment

Glucose

Basal glycemia: glycogenolysis, gluconeogenesis

Constant regulation of glycemia in moderate adjustments

Starter energya to initiate adaptation

Evaluate relative to adrenaline (rapid, large adjustments of glycemia): children: adrenaline > glucagon, adults: glucagon > adrenaline

Lipolysis

Beta-oxidation for ATP production

Lipids a

A starter engine is a noncombustion engine that starts the combustion engine so that it can run the car per the demands of the driver.

Insulin: Endocrine pancreas Insulin is the restorative hormone, counteracting catabolic actions of both loops, growth-promoting hormone par excellence. It is involved in the utilization, preservation, and storage of nutrients but has unique functions in the brain (Table 6.5).

Integrating the somatotropic axis First loop 1. Central: a. GHRH stimulates GH b. GH: i. Increases circulating free fatty acids ii. Increases uptake of minerals, amino acids iii. Stimulates hepatic IGF-1 excretion iv. Stimulates Prolactin (turn the loop, prepare for insulin) v. Installs insulin resistance (prevent early closing of anabolism by insulin) vi. Inhibits GHRH by classical feedback c. PL: Turns the loop

2. Peripheral: IGF-1 a. Initiates growth b. Prepares cell for insulin c. Inhibits GH by classical feedback Second loop 1. Central a. TRH i. Stimulates PL ii. Stimulates Insulin b. PL i. Inhibits GH, releases insulin resistance from insulin receptors ii. Stimulates Insulin 2. Peripheral a. Insulin i. Conserves carbohydrates, proteins and lipids ii. Provides substrates for ATP production iii. Stimulates growth of cell, finalizes all that was prepared preceding it iv. Closes the door of anabolism

TABLE 6.5  Conservative effects of insulin Substance/location

Utilization

Preservation

Storage

Carbohydrates

Glucose entry into cells

Inhibits glycogenolysis

Glycogenesis

Lipids

Free fatty acid entry into cells

Blocks lipolysis

Lipogenesis

Proteins

Blocks proteolysis

Blocks gluconeogenesis (from amino acids)

–

Electrolytes

Potassium entry into cells

Diminishes renal sodium excretion

–

Cell

–

Reduces autophagy of organelles

–

Cardiovascular

Vasodilator: improves microvascular flow for nutrient distribution

–

–

Brain

–

Synaptic plasticity

Memory: formation, consolidation, recall

126  The theory of endobiogeny

3. Central/Peripheral a. Somatostatin i. Inhibits all somatotropic hormones and central thyrotropic hormones that relaunch the somatotropic axis: 1. GHRH 2. PL 3. IGF-1 4. Insulin 5. TSH

Pathophysiology As with the gonadotropic axis, the somatotropic is most implicated in the structural formation and maintenance of the endoderm. This includes structures such as the liver, pancreas, and lungs. However, pathophysiologic conditions related to dysfunction of the somatotropic axis are not limited to this embryonic lineage, which refers to structural formation. It touches all tissues and all functions because of its role in structural activity and adaptation. Thus, imbalances related to the axis can be broadly divided into disorders structural integrity, structural adaptation, and function. The gonadotropic and somatotropic axis are typically implicated in structural disorders. In functional disorders, the two catabolic axes are implicated: corticotropic and thyrotropic. The somatotropic axis is also implicated in adaptation because of the role of glucagon which is why it is also implicated in disorders of adaptation, structuro-functional, and global (Table 6.6).

Symptoms related to the somatotropic axis Because the axis plays a role in so many fundamental aspects of structure, function, adaptation, and personality,

there are numerous symptoms reported by the patient or elicited by the physician that relate to this axis (Table 6.7).

Signs related to the somatotropic axis Signs related to the axis are more numerous than symptoms. The somatotropic axis plays a key role in formation of structure and function. One can observe temperament (Table 6.8) related to the axis. On examination, one can look for signs related to the skin (Table 6.9), head (Table 6.10), mouth (Table  6.11), chest and breasts (Table  6.12), abdomen (Table 6.13), back and skeletal system (6.14).

Biology of function indexes related to the somatotropic axis The greatest number of hormones and varieties of actions related to metabolism are within the somatotropic axis. It is no surprise then that the indexes of this axis are the most numerous of those of the four endocrine axes. The indexes are drawn from numerous biomarkers and indexes. Chief among them are osteocalcin1–5 and alkaline phosphatase bone isoenzymes,6–8 both biomarkers derived from bone. The bone serves as an indicator of global metabolism and these biomarkers are related to global intracellular function (The Theory of Endobiogeny, Volume 1, Chapter 15).7–9 In turn, they are both related to growth hormone activity.7 In addition to these two biomarkers, TSH, a pro-anabolic factor that happens to stimulate the thyroid gland, is also key. The higher the serum TSH, the more anabolic activity of the somatotropic axis tends to be at the level of global management (Tables 6.15–6.17). The inverse will be true for intracellular functions such as oxidation of glucose and mitochondrial function. There is a dialectic between ­osteocalcin

TABLE 6.6  Pathophysiology related to the somatotropic axis Category

Subcategory

Example

Structural adaptation

Adenosis

Polyps

Cysts

Breast, ovary, kidney, brain, pancreas, ganglion, etc.

Fibroids

Leiomyoma of uterus

Hyperplasia

Cancer, obesity

Hypertrophy

Cancer, obesity, tonsil hypertrophy

Lipomas

Lipomas

Cicatrization

Keloids, delayed wound healing

Cellular metabolism

Diabetes, hypoglycemia

Neurologic metabolism

Multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, sphingolipidosis

Inflammation

General fragilization of terrain

Functional adaptation

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TABLE 6.7  Symptoms related to the somatotropic axis by region Category

Finding

Factor

State

Dermatologic

Purulent acne

Prolactin

Hyperfunctioning

Eczema

Pancreas

Oversolicited

ENT

Recurrent sinusitis, tonsil infections

Pancreas

Oversolicited

Breast

Breast milk, abundant postpartum

Prolactin

Strong

Perimenstrual lactation

Prolactin

Excessive

Increased appetite

Insulin

Predominant

Dislike of fruit

Insulin

Excessive

With low insulin resistance

Hypoglycemia

Insulin

Hyperfunctioning

with low insulin resistance; may present as hyperglycemia on fasting measurement with normal HgA1c

Bloating

Pancreas

Congested

Chronic gastritis

Pancreas

Congested

Anal fissures

Pancreas

Congested

Hemorrhoids

Pancreas

Congested

Menstrual cycle, irregular

Prolactin

Insufficient

Libido, strong during luteal phase

Prolactin

Strong

Menstrual cycle blocked

Prolactin

Excessive or hyperfunctioning

Amenorrhea

Prolactin

Excessive or hyperfunctioning

General feeling of coldness

Prolactin

Excessive and predominant

General fatigue

Prolactin

Insufficient

In corticotropic relaunching

Weight gain

Prolactin

Insufficient or excessive

In corticotropic relaunching

Diabetes

Insulin

Diminished function

Typically, hypersecreted; function is diminished in glucose delivery but hyperfunctioning in lipid management

Weight gain

Insulin

Diminished function

Typically, hypersecreted; function is diminished in glucose delivery but hyperfunctioning in lipid management

Bone

Osteoporosis

Prolactin

Excessive

Favoring inflammation and osteoclasty

Oncology

Angioneogenesis and cancer growth

Prolactin

Hyperfunctioning

Rheumatology

Autoimmunity: polyarthritis

Prolactin

Hyperfunctioning

Gastrointestinal

Genitourinary

Metabolic

Comment

Correlate with strong FSH and TSH with latent hypothyroidism

In conjunction with TRH and general central hyperthyroidism and typically prolonged relaunching of corticotropic axis and cortisol

TABLE 6.8  Signs of temperament related to the somatotropic axis Quality

Finding

Factor

Activity

Comment

External

Social tendency

Growth hormone

Prominent

Desire to gather people for their mutual benefit

External

Fear

Prolactin

Excessive

Correlate with strong central alpha

Internal

Poor adaptation to stress

Prolactin

Hyperfunctioning

Evaluate for signs of weak cortisol, weak ACTH

Internal

Maternal feeling

Prolactin

Prominent

Evaluate for signs of strong estrogen, strong oxytocin (erect nipple)

Internal

Lack of maternal feeling

Prolactin

Ineffectual

Evaluate for signs of weak cortisol, weak ACTH

TABLE 6.9  Dermatologic signs related to the somatotropic axis Quality

Finding

Factor

Activity

Comment

Subcutaneous tissue

Infiltrated, dense, woody

Prolactin

Prominent

Correlate with thyroid function and lymphatic congestion

Acne

Pus

Prolactin

Hyperfunctioning

Freckles

Present

Prolactin

Prominent

An oversolicitation of weak or below-average adrenals, with peripheral blockage of MSH

Furuncle

Present

Prolactin

Excessive

A deep folliculitis

Keratosis

Present

GH

Hyperfunctioning

With hyperandrogenism that relaunches FSH, excess estrogen + latent hypothyroidism: elevated TSH + peripheral thyroid insufficiency

Scar

Pruritic

GH

Hyperfunctioning

Skin color

Pale, milky

Prolactin

Prominent and hyperfunctioning

Nail thickness

Thick and strong

GH

Predominant

Nail deformity

Pitting

GH

Overfunctioning

Can also be sign poor hepatic absorption of nutrients (correlate with scalloped tongue)

TABLE 6.10  Signs of the head related to the somatotropic axis Quality

Finding

Factor

Activity

Hair

Ability to grow long

GH

Strong

Brow

Prominent

GH

Prominent

Postpubertal GH expression; when it is stimulated by TRH, the number of GH receptors is increased

Eyelashes

Thick, overlapping

GH

Prominent

Arises from an appeal of FSH to GH; in children and women, because they have fewer adrenal androgens, the effects of GH are more pronounced, hence the thicker eyelashes

Thinly spaced

GH

Not prominent

Insufficient stimulation of intracellular growth factors by FSH

Polyp

GH

Hyperfunctioning

Implies elevated insulin activity

Length of osseous portion

Insulin

Prominent

Correlate with strong thyroid and/or strong cortisol activity; increased metabolic activity demands a longer period of respiration, which requires a larger antechamber for the nose

Length of cartilaginous portion

GH

Prominent

Reflects delayed end of growth; correlate to strong cortisol, weak somatostatin, weak thyroid activity, elevated insulin resistance and other factors

Bulbous

GH

Excessive

GH adapted to parasympathetic insufficiency in the face of strong cortisol

Nose

Comment

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TABLE 6.11  Signs of the mouth related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

Lips

Size

Full, thick

Pancreas

Congested

Implies elevated para

Mucosa, oral

Ulceration

Aphthous ulcer

GH

Hyperfunctioning

Teeth

Spacing

Widely spaced

GH

Strong

Tongue

Fissures

Fissures

GH

Hyperfunctioning

Tongue

Size

Large, thick, with dental impression

Growth hormone

Excessive

Growth hormone compensation in the tissular nutrition activity to compensate for hypothyroidism; GH congests the splanchnic circulation to augment nutrient absorption, which leads to glossal edema

Uvula

Shape

Bifid

Somatotropic

Excessive

Growth factors > antigrowth, resulting in a TSH relaunching of the thyroid (hyperthyroid state), resulting in strong ACTH/ LH to maintain strong TSH stimulation of the thyroid

Tonsils

Size

Hypertrophy

Pancreas

Congested

Congestion, pancreas

Tonsils

Color

Erythema

Pancreas

Congested

Congestion, pancreas

Tonsils

Coating

Coating, white

Colon

Congested

Congestion, colon

Postpubertal GH expression

TABLE 6.12  Signs of the chest and breast related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

Sternum

Orientation

Convex

GH

Hyperfunctioning

Correlate with PTH

Breast

General

Underdeveloped

Prolactin

Diminished in structure

Size

Voluminous and dense

Prolactin

Prominent

Erection

Erect

Prolactin

Hyperfunctioning

Size

Large

Prolactin

Prominent

Duct

Expression

Prolactin

Excessive

Nipple

Often voluminous; cause is prolactin, consequence is elevated insulin/ weak insulin resistance and strong estrogen and androgens

May also be hyperfunctioning

TABLE 6.13  Signs of the abdomen related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

General

Proximal

Adiposity, doughy

Insulin

Excessive and typically reactive and hyperfunctioning

Correlate with elevated cortisol and altered insulin resistance

Pancreas

Mid-point between umbilicus and xyphoid

Pain on palpation

Pancreas

Congestion

Congestion, pancreas

Pancreas

Medial-right from umbilicus

Pain on palpation

Pancreas

Exocrine congestion

Congestion, pancreas, exocrine

Pancreas

Medial-left from umbilicus

Pain on palpation

Pancreas

Endocrine overtaxed

Congestion, pancreas, endocrine

Colon

Descending, distal

Pain on palpation

GH

Oversoliciting

TABLE 6.14  Signs of the back, extremities, and bones related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

Scapula, right

Inferior-medial, T6-7

Pain on palpation

Liver

Congested

Congestion, liver

Scapula, left

Inferior-medial, T7-T8

Pain on palpation

TSH, PL

Oversoliciting

Congestion, colon, transverse and descending

T7-T10

Paraspinal

Pain on palpation

Endocrine pancreas

Congested

Chronic congestion

Hand

Dorsum

Edematous

Prolactin

Hyperfunctioning

Knee, right

Thickness

Thick knee

FSH-TSH-GH

Overfunctioning

Foot

Shape

Hallux valgus (bunion)

GH

Excessive

Foot

Dorsum

Edematous

Prolactin

Hyperfunctioning

Foot

Arch

Flat

Prolactin

Predominant, likely excessive

Bone

Width

Wide

Prolactin

Prominent

Bone

Length

Long

GH

Prominent

Postpubertal

TABLE 6.15  Indexes assessing central somatotropic activity Relationship Index

Definition

Import

Direct

Inverse

Correlations

GH growth score

It calculates the level that results from the endocrinometabolic activity of growth hormone. By extension, it evaluates the role played by the somatotropic axis in the general adaptation syndrome and in the summoning and distribution of structural and functional energy

High: increased utilization of nutrients, risk of adenoidal growths Low: risk of somatotropic desynchronization due to a hyperalpha and/or central hyperthyroid activity

Growth score

Growth score corrected

Antigrowth index Adenosis index

Prolactin

It expresses the level of prolactin activity. It witnesses the level of solicitation of the general adaptation syndrome of Endobiogeny and its systematized modules

High: prolactin is active in turning the first loop in order to relaunch cortisol Low: prolactin is either diminished by central somatostatin and/or not required due to the quality of cortisol activity

Somatostatin

Growth hormone index

High: serum TSH, cortisol index Low: dopamine activity, cortisol index

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TABLE 6.16  Indexes assessing peripheral somatotropic activity Relationship Index

Definition

Import

Direct

Inverse

Somatostatin

It expresses the level of activity of somatostatin; indirectly it witnesses the relative level of activity of the exocrine pancreas

High: exocrine pancreas oversolicited and contributing to disorders of excess nutrients and hypertrophic growth Low: insufficient exocrine pancreas activity, somatostatin allows for prolonged endocrine activity and hyperplastic growth

Antigrowth index

Cortisol

Insulin

It measures the level of functional endocrinometabolic activity of the insulin

High: hyperinsulinism, risk of somatotropic desynchronization Low: hyperinsulinism due to insufficient membrane sensitivity

Catabolism/ anabolism Cortisol

Insulin resistance

It measures the level of inhibition of insulin at membrane level, independently of the temporary inhibition linked to adaptation syndrome

Low: organism may be compromised in distribution of glucose to vital organs High: favors prolonged first loop activity, risk of nourishment of vital organs at expense of other organs and tissues

Growth index corrected

It expresses the intracellular activity of growth factors

It evaluates the role of IGF-1 and other growth factors

Alkaline phosphatase bone isoenzyme

Correlations

Insulin resistance Redox Harmful free radicals Insulin Cortisol

Redox Harmful free radicals

Osteocalcin

Antigrowth, demyelization, membrane expansion

TABLE 6.17  Indexes assessing general metabolic effects of somatotropic hormones Relationship Index

Definition

Import

Direct

Inverse

Correlations

Catabolism

It measures the level of catabolic activity of the organism

Catabolism nourishes anabolism

Thyroid index

Adrenal cortex index

Genitothyroid Catabolismanabolism

Anabolism

It measures the level of anabolic activity of the organism

Anabolism ensures the restoration of the organism

Catabolism

Catabolismanabolism

Metabolic yield

It measures the overall metabolism rate of the organism

It expresses the general degree of efficacy of the organisms be it in its level of production or repartitioning

Catabolism, anabolism

Ischemia, membrane fracture

Ischemia

It measures the level of tissular congestion relative to the cell metabolic activity

Demyelination index corrected

It expresses the relative level of adaptability of the energeticometabolic response of insulin in its chronologic rapport to that of the endocrine activity of growth hormone

Adenosis

It measures the degree of relative activity of endocrine factors propitious for hyperplasia

Bone remodeling

Metabolic yield

Splanchnic congestion

High: desynchronization of somatotropic activity with insulin preceding growth factors

Insulin index

Growth index corrected

Amylosis Somatostatin

High: it captures all the events that solicit an organ to augment its yield, its rate of production and its volume. It favors a terrain for all adenoidal growths

Osteocalcin

Ischemia index, TRH/ TSH index

132  The theory of endobiogeny

and TSH reflected in the indexes, as they vary inversely with each other.6, 10, 11 The lower the osteocalcin, the greater intracellular metabolism tends to be for a given serum TSH. The prolactin index is currently the only strictly central somatotropic index in the biology of functions (Table 6.15). Dr. Duraffourd created it to evaluate how prolactin plays a role in solicitation of the adaptation syndrome and its role in turning the first loop and by extension how effectively somatostatin is able to downregulate prolactin at the end of the second loop. The GH (growth hormone) growth score does not evaluate the endocrine function of GH with regard to production of insulinlike growth factor 1 (IGF-1) in the liver. It evaluates the role of GH in the timing and distribution of nutrients, which is an endocrinometabolic activity. The index is low in disorders of somatotropic desynchronization such as Crohn’s disease, multiple sclerosis, chronic fatigue syndrome, and fibromyalgia. It is elevated in disorders of hypertrophy and hyperplasia such as adenoidal growth such as of the breast or prostate and in diabetes mellitus type two. It is normally several fold elevated during normal pediatric growth. The somatostatin index (Table 6.16 and The Theory of Endobiogeny, Volume 2, Chapter 8) is evaluating peripheral somatostatin activity and by extension central activity is inferred. There are a number of indexes that evaluate the function of strictly peripheral somatotropic activity related to distribution of nutrients. The activity of glucagon from alpha-islet cells of the endocrine pancreas is discussed under the discussion of indexes related to the autonomic nervous system, because of its role in adaptation (The Theory of Endobiogeny, Volume 2, Chapter  1). We discuss here four key indexes. The first is somatostatin, excreted from delta-islet cells of the endocrine pancreas and other areas of the gastrointestinal tract. Strictly speaking, the index evaluates peripheral somatostatin activity and its role in ending growth.12–15 This occurs in two ways: installing an antigrowth milieu, and inhibiting excretion of digestive enzymes. Thus, the index evaluates the actions of somatostatin on the exocrine pancreas. Cortisol inhibits excretion of digestive enzymes but also inhibits somatostain.16–19 The index effectively evaluates the relative role of somatostatin vs cortisol and the competency of the exocrine pancreas. Somatostatin ends exocrine pancreas activity because it is prolonged or excessive. Cortisol inhibits it, diminishing the exocrine pancreas’ ability to play its proper role in nutrient extraction and all that that implies. The evaluation of beta-islet cell endocrine pancreas activity is through the insulin index (Table 6.16). The insulin resistance index, technically speaking, is an evaluation of the intracellular, inner membrane response to insulin activity on the outer portion of the membrane. It is included here to complete the arc of activity within the pancreas. Finally, there are indexes evaluating the role of growth and antigrowth factors. Here we discuss the growth index corrected. It corrects the evaluation of growth hormone’s metabolic

effects on cellular function to account for the role of other intracellular growth factors. There are numerous indexes evaluating a general metabolic activity regulated by the somatotropic axis. The catabolism/anabolism index is discussed with the indexes of the corticotropic axis (The Theory of Endobiogeny, Volume 2, Chapter 2). That index is evaluating the relative predominance of catabolism in relationship to that of anabolism. In the somatotropic axis we have the quantitative estimation of catabolism and anabolism individually (Table 6.17). The catabolism index is formed by the ratio of thyroid metabolic activity in relationship to that of global adrenal cortex activity. Peripheral thyroid hormone activity favors catabolism, especially T4. Adrenal cortex activity, particularly the anabolic hormones, if excessive, will try to initiate anabolism before catabolism is completed. This diminishes catabolic achievement. Since catabolism feeds anabolism according to the theory of Endobiogeny, it will diminish anabolic achievement as well (The Theory of Endobiogeny, Volume 1, Chapter  6). The anabolism index contains the catabolism index in its numerator. The greater the rate of catabolism, the greater the rate of material presented for anabolism will be. The metabolic yield is simply the sum effects of both catabolism and anabolism. The demyelination index evaluates the risk of loss of the myelin sheath due to somatotropic desynchronization. This index is particularly helpful evaluating symptoms of neuropathy and chronic pain. The adenosis index evaluates the risk of adenoidal growth, which is a type of hyperplastic growth. Hyperplasia is a growth in the number of cells. It reflects a thyro-somatotropic relationship based in a latent or expressed hypothyroidism in the face of augmented somatotropic growth activity. Cells and tissues have an intrinsic metabolism that is regulated by assessment of intrinsic needs. Because they are situated in a global environment, the endocrine system adapts the intrinsic function to the needs of regional or global metabolism. Of all the axes, the somatotropic influenced by TSH is the most influential. The indexes discussed in Table  6.17 a general indication of the direction and magnitude of growth. There are consequences to this that refer to the method in which the cell obtains nutrients and electrolytes, and the degree to which they are oxidized or utilized in some other fashion. The indexes in Table 6.18 discuss these activities. Active cell permeability refers to the transport of substances into the cell through pores and channels in an active manner, meaning with the use of ATP to drive movement against its gradient. Passive permeability refers to the diffusion of substances or their movement down a concentration gradient. It is proportional to the membrane fluidity of the cell membrane20 and typically refers to the movement of small, nonpolar molecules.21 This distinction is significant because only the first method can be regulated. The second cannot. In states of hypertrophy or hyperplasia, one

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TABLE 6.18  Indexes assessing cellular metabolic activity as regulated by somatotropic hormones Relationship Index

Definition

Import

Direct

Inverse

Correlations

Active cell permeability

It measures the degree of dynamic activity of cross-membrane permeability

High: favors first loop nutrition via membranebound channels

TSH

Insulin

Somatostatin

Passive cell permeability

It measures the degree of strictly osmotic cross-membrane permeability

Low: favors insufficient membrane fluidity

Necrosis; adaptation permissivity

No denominator

Redox

it measures the global oxidoreduction activity of the organism

Low: favors impaired response to microbial infections

Insulin index

Somatostatin index

Noxious free radicals

it measures the global rate of circulating free radicals

Pro-amyloid index

It measures the level of intra-cell hypometabolism. By extension, it evaluates the degree of cellular respiratory insufficiency and the degree of nutritional insufficiency

High: favors mitochondrial insufficiency

wishes to regulate the rate and magnitude of nutrient entry. Disorders such as diabetes will have elevated active permeability and diminished passive permeability. In this case, the use of a higher protein, lower carbohydrate diet, will prove more beneficial in our experience. In disorders such as chronic fatigue syndrome and neuropathy, the inverse is found: too much passive diffusion and insufficient active diffusion. The cell membrane is too fluid. Anecdotally, we have observed that a whole grain, high fiber diet with fish or vegetarian proteins is more corrective of this situation. Redox is the sum of reduction and oxidation of glucose and lipids for ATP production. It is the consequence of the quality of insulin activity, somatostatin, and membrane permeability. Excessive redox favors inflammation and free radicals, both beneficial and harmful.22 Insufficient redox can play a role in compromised immunity, or, the reliance on ketones and other substances for energy. It increases the risk of mitochondrial insufficiency, reflected in the proamyloid index. The mitochondrion plays a key role in cell health and nucleus regulation.23

Conclusions The somatotropic axis has many levels of function. It is a fashioner of structure in its material crystallization. It is a regulator of structural activity of the cell related to its intrinsic maintenance of its material structure. The axis regulates the structuro-functional adaptation of cellular activity and its participation in functional adaptation. The axis plays a role in

Oxidoreduction index

DNA fracture

Insulin resistance

Reduction index

the entire ecology of metabolism in its general sense of the rate of function and the particular sense of nutrient apportionment, distribution and timing of entry and utilization. There are many aspects of somatotropic function that can be determined by history, examination, and biology of functions. The axis plays a role in disorders ranging from cancer to chronic fatigue, from diabetes to multiple sclerosis. A proper assessment of somatotropic function allows from a regulation of disorders of structure, adaptation, and metabolism.

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134  The theory of endobiogeny

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