Also see:
W.D. Denckla, A.V. Everitt, Hypophysectomy, & Aging
Removal of the Pituitary: Slows Aging and Hardening of Collagen
“Normal” TSH: Marker for Increased Risk of Fatal Coronary Heart Disease
Thyroid Insufficiency. Is Thyroxine the Only Valuable Drug?
High T4 Concentrations in the Brain – Suppression of Brain Metabolism
Assessment of the Thyroid: Achilles Tendon Reflex
Thyroid Status and Cardiovascular Disease
The Cholesterol and Thyroid Connection
High Blood Pressure and Hypothyroidism
A Cure for Heart Disease
Hypothyroidism and A Shift in Death Patterns
High Cholesterol and Metabolism
Growth Hormone and Edema
Quotes by Ray Peat, PhD
“TSH has direct actions on many cell types other than the thyroid, and probably contributes directly to edema (Wheatley and Edwards, 1983), fibrosis, and mastocytosis. If people are concerned about the effects of a TSH “deficiency,” then I think they have to explain the remarkable longevity of the animals lacking pituitaries in W.D. Denckla’s experiments, or of the naturally pituitary deficient dwarf mice that lack TSH, prolactin, and growth hormone, but live about a year longer than normal mice (Heiman, et al., 2003). Until there is evidence that very low TSH is somehow harmful, there is no basis for setting a lower limit to the normal range.”
“W.D. Denckla discovered that the pituitary hormones are in some way able to accelerate the process of aging…Removing animals’ pituitaries, Denckla found that their aging was drastically slowed.”
“Denckla’s experiments are reminiscent of many others that have identified changes in pituitary function as driving forces in aging and degenerative diseases.”
“When W. Donner Denckla demonstrated that the removal of an animal’s pituitary (or, in the case of an octopus, its equivalent optic gland) radically extended the animal’s life span, he proposed the existence of a death hormone in the pituitary gland.”
“While Arthur Everitt, Verzar, and others were studying the effects of the rat’s pituitary (and other glands) on collagen, W. D. Denckla investigated the effects of reproductive hormones and pituitary removal in a wide variety of animals, including fish and mollusks. He had noticed that reproduction in various species (e.g., salmon) was quickly followed by rapid aging and death. Removing the pituitary gland (or its equivalent) and providing thyroid hormone, he found that animals lacking the pituitary lived much longer than intact animals, and maintained a high metabolic rate. Making extracts of pituitary glands, he found a fraction (closely related to prolactin and growth hormone) that suppressed tissue oxygen consumption, and accelerated the degenerative changes of aging…A high level of respiratory energy production that characterizes young life is needed for tissue renewal. The accumulation of factors that impair mitochondrial respiration leads to increasing production of stress factors, that are needed for survival when the organism isn’t able to simply produce energetic new tissue as needed. Continually resorting to these substances progressively reshapes the organism, but the investment in short-term survival, without eliminating the problematic factors, tends to exacerbate the basic energy problem. This seems to be the reason that Denckla’s animals, deprived of their pituitary glands, but provided with thyroid hormone, lived so long: they weren’t able to mobilize the multiple defenses that reduce the mitochondria’s respiratory energy production.”
“The “little mouse,” and the experiments of Denckla and Everitt, show that a simple growth hormone deficiency or lack of pituitary function can double the life span: Intervention in the many other self-stimulating excitatory pathways can produce additional retardation of the aging process, acting at many levels, from from the extracellular matrix to the brain.”
“A mutant dwarf mouse, called “little”, has only 5% to 10% as much growth hormone as normal mice, and it has an abnormally long lifespan.”
“The metabolic rhythm should correspond to the light-dark rhythm, because darkness is a basic biological stress, and sleep is protective against the stress of darkness. Since TSH has many maladaptive effects, and rises along with prolactin and cortisol during the night, some thyroid taken at bedtime helps to reduce the stress, moderating the TSH rise while keeping the blood sugar from falling too fast. Ice cream (i.e., sugar and fat with a little protein) at bedtime has a similar effect, reducing the rise of adrenaline, cortisol, etc., with the result that the morning cortisol peak will be lower, preferably below the middle of the common range, and then it should decline in the afternoon.”
Endocrine. 2003 Feb-Mar;20(1-2):149-54.
Body composition of prolactin-, growth hormone, and thyrotropin-deficient Ames dwarf mice.
Heiman ML, Tinsley FC, Mattison JA, Hauck S, Bartke A.
Ames dwarf mice have primary deficiency of prolactin (PRL), growth hormone (GH), and thyroid-stimulating hormone (TSH), and live considerably longer than normal animals from the same line. In view of the documented effects of GH, PRL, and thyroid hormones on lean and fat body mass and skeletal growth, and the suspected relationship of body size and composition to life expectancy, it was of interest to examine age-related changes in body composition of Ames dwarf mice. Lean mass, fat mass, bone area, and bone mineral content (BMC) were determined in dwarf and normal mice at the ages of 2, 4.5 6, and 18 mo using dual X-ray absorptiometry. In addition to the expected significant declines in lean mass, bone area, and BMC, dwarf mice exhibited attenuation of the age-related increase in bone mineral density and delayed or attenuated increase in percentage of body fat. Percentage of body fat was lower in adult dwarfs than in the corresponding normal controls. Patterns of age-related changes in body composition in Ames dwarf mice are consistent with the recent report of age-related changes in body composition in PRL receptor knockout mice. We suspect that reduction in relative adiposity may contribute to the previously reported increase in insulin sensitivity of Ames dwarf mice and thus may be a factor in delayed aging and increased longevity of these animals.
“W.D. Denckla’s version of programmed aging proposed that the pituitary gland was the agent of this programmed aging. He based his idea on the observation that when animals were kept on a semi-starvation diet, starting before puberty, their puberty was delayed and they lived longer than normal, and on later studies showed that when animals’ pituitary glands were removed before puberty, they lived much longer than normal, and all of their tissues and systems aged at a much slower rate. The implication was that if the gland is present and causes aging, its evolutionary purpose is to cause aging, as well as the other process such a reproduction.
The particular function that Denckla focused on as an index of aging was oxygen consumption, which decreases by more than 70% between puberty and old age. He showed that the decrease of oxygen consumption was much less when the pituitary gland was removed, if the animal was given the amount of thyroid hormone that it would normally produce. He found fairly specific pituitary extracts that decreased oxygen consumption, inhibiting the effects of the thyroid hormone, but he never identified a particular pituitary hormone as the antirespiratory aging hormone, or the mechanism responsible for the extract’s effects.” -Ray Peat, PhD
J Clin Invest. 1974 February; 53(2): 572–581.
Role of the pituitary and thyroid glands in the decline of minimal O2 consumption with age.
W D Denckla
Resting O2 consumption rate (BMR) or minimal O2 consumption rate (MOC) declines with age. Data are presented that suggest that a newly described function of the pituitary may be responsible for a considerable part of the total 75% decline in the MOC with age. The new function appears to decrease the responsiveness of peripheral tissues to thyroid hormones. Response curves to injected thyroxine indicated that immature rats were three times more responsive to thyroxine than adult rats. All the major endocrine ablations were performed in this and earlier work, and only pituitary ablation (a) restored in adults part of the responsiveness to thyroxine found in immature rats and (b) arrested the normal age-associated decrease in responsiveness to thyroxine in immature rats. Bovine pituitary extracts were found that decreased the responsiveness of immature rats to thyroxine. Experiments with the new pituitary function suggested a possible endocrine mechanism to explain why partial starvation doubled the lifespan for rats only when started before puberty.
Fed Proc. 1975 Jan;34(1):96.
Pituitary inhibitor of thyroxine.
Denckla WD.
A description is given of a new pituitary function. It is suggested that the new function acts to decrease gradually the responsiveness of the peripheral tissues to thyroid hormones throughout life. It is suggested that the postulated relative hypothyroidism of older animals might contribute to their loss of viability.
Clin Endocrinol (Oxf). 1983 Jun;18(6):627-35.
Mild hypothyroidism and oedema: evidence for increased capillary permeability to protein.
Wheatley T, Edwards OM.
Nine female patients with normal serum total thyroxine (T4) and triiodothyronine (T3) but elevated thyroid stimulating hormone (TSH) levels were studied. Six patients had generalised oedema associated with maximal diurnal weight gains in excess of 1.4 kg. Under conditions of forced water diuresis, before and during physiological replacement of 1-thyroxine, the supine transcapillary escape rate of albumin (TERA) was measured, while the venous colloid osmotic pressure (COP), packed cell volume (PCV) and urinary excretion of water and electrolytes were studied in both the supine and upright positions. The TERA, diurnal weight gain and orthostatic increase in COP fell significantly with treatment. In the six patients with oedema and excessive diurnal weight gains, the retention of salt and water on tilting was reduced with thyroxine treatment. In female patients we consider generalised oedema associated with excessive diurnal weight gain, to be a common and early symptom of hypothyroidism, meriting thyroxine replacement therapy.
