Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone.

A cross-sectional survey was made in 56 exceptionally healthy males, ranging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cognitive and physical tests were performed. Of those blood serum variables that gave highly significant negative correlations with age (r > -0.6), bioavailable testosterone (BT), dehydroepiandrosterone sulfate (DHEAS), and the ratio of insulin-like growth factor 1 (IGF-1) to growth hormone (GH) showed a stepwise pattern of age-related changes most closely resembling those of the age steps themselves. Of these, BT correlated best with significantly age-correlated cognitive and physical measures. Because DHEAS correlated well with BT and considerably less well than BT with the cognitive and physical measures, it seems likely that BT and/or substances to which BT gives rise in tissues play a more direct role in whatever processes are rate-limiting in the functions measured and that DHEAS relates more indirectly to these functions. The high correlation of IGF-1/GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1/GH and BT with significantly age-correlated cognitive and physical measures suggest that the GH-IGF-1 axis and BT play independent roles in affecting these functions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of steroid metabolic systems with those operational in control of interrelations in the GH-IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1/GH together with detailed studies of their correlations with age-correlated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.

[1]  Z. Barrou,et al.  Dehydroepiandrosterone (DHEA) and aging. , 1997, Archives of gerontology and geriatrics.

[2]  W. Miller,et al.  The regulation of 17,20 lyase activity , 1997, Steroids.

[3]  E. Baulieu,et al.  Dehydroepiandrosterone (DHEA): a fountain of youth? , 1996, The Journal of clinical endocrinology and metabolism.

[4]  J. Morley,et al.  Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: the amygdala is by far the most sensitive. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  E. Roberts Pregneolone--from Selye to Alzheimer and a model of the pregnenolone sulfate binding site on the GABAA receptor. , 1995, Biochemical pharmacology.

[6]  L. Guth,et al.  Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. Castro-Alamancos,et al.  Learning of the conditioned eye-blink response is impaired by an antisense insulin-like growth factor I oligonucleotide. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Yen,et al.  Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. , 1994, The Journal of clinical endocrinology and metabolism.

[9]  A. Morales Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age [published erratum appears in J Clin Endocrinol Metab 1995 Sep;80(9):2799] , 1994 .

[10]  I. Torres-Aleman,et al.  Orthograde transport and release of insulin‐like growth factor I from the inferior olive to the cerebellum , 1993, Journal of neuroscience research.

[11]  S. W. Parker Vestibular Evaluation — Electronystagmography, Rotational Testing, and Posturography , 1993, Clinical EEG.

[12]  L. Cacicedo,et al.  Pituitary and Peripheral Insulin‐like Growth Factor‐I Regulation by Thyroid Hormone a , 1993, Annals of the New York Academy of Sciences.

[13]  M. Fischer,et al.  Steroid binding to human serum albumin and fragments thereof. Role of protein conformation and fatty acid content. , 1993, Biochemical pharmacology.

[14]  H. Perry,et al.  Effects of Testosterone Replacement Therapy in Old Hypogonadal Males: A Preliminary Study , 1993, Journal of the American Geriatrics Society.

[15]  I. Torres-Aleman,et al.  Climbing fiber deafferentation reduces insulin-like growth factor I (IGF-I) content in cerebellum , 1991, Brain Research.

[16]  C. Alessi,et al.  Low serum free thyroxine index in ambulating elderly is due to a resetting of the threshold of thyrotropin feedback suppression. , 1991, The Journal of clinical endocrinology and metabolism.

[17]  D. Leszczynski,et al.  Metabolic conversion of six steroid hormones by human plasma high-density lipoprotein. , 1991, Biochimica et biophysica acta.

[18]  S. S. Davis,et al.  Secondary hypogonadism in older men: its relation to impotence. , 1990, The Journal of clinical endocrinology and metabolism.

[19]  A. Damasio,et al.  Alzheimer's dementia: performance on parallel forms of the dementia assessment battery. , 1989, Journal of clinical and experimental neuropsychology.

[20]  L. Parker Adrenal Androgens in Clinical Medicine , 1989 .

[21]  W L Miller,et al.  Molecular biology of steroid hormone synthesis. , 1988, Endocrine reviews.

[22]  J. Robben,et al.  Isolation and identification of intestinal steroid-desulfating bacteria from rats and humans , 1988, Applied and environmental microbiology.

[23]  P. Chang,et al.  Tissue-specific expression of human arylsulfatase-C isozymes and steroid sulfatase. , 1987, American journal of human genetics.

[24]  H. Nankin,et al.  Decreased bioavailable testosterone in aging normal and impotent men. , 1986, The Journal of clinical endocrinology and metabolism.

[25]  R. Hobkirk Steroid sulfotransferases and steroid sulfate sulfatases: characteristics and biological roles. , 1985, Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire.

[26]  W. Cefalu,et al.  Bioavailability of albumin-bound testosterone. , 1985, The Journal of clinical endocrinology and metabolism.

[27]  F. Peillon,et al.  Correlative studies between the presence of thyrotropin-releasing hormone (TRH) receptors and the in vitro stimulation of growth-hormone (GH) secretion in human GH-secreting adenomas. , 1985, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[28]  R. Nass,et al.  The assessment of aphasia and related disorders By Harold Goodglass and edith kaplan philadelphia, lea & febiger, 1983 illustrated, $27.50 (package) , 1984 .

[29]  D. Mungas Differential clinical sensitivity of specific parameters of the Rey Auditory-Verbal Learning Test. , 1983, Journal of consulting and clinical psychology.

[30]  J. Chaussain,et al.  Prolactin and thyrotrophin responses to thyroliberin (TRH) in patients with growth hormone deficiency: study in 167 patients. , 1983, Acta endocrinologica.

[31]  L. Milewich,et al.  Metabolism of androstenedione by human platelets: a source of potent androgens. , 1982, The Journal of clinical endocrinology and metabolism.

[32]  Alfred W. Kaszniak,et al.  Remote Memory in Senile Dementia , 1981, Cortex.

[33]  H. Imura,et al.  Age-related changes of serum 3,3'-diiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine concentrations in man. , 1981, The Journal of clinical endocrinology and metabolism.

[34]  V. J. Wilson,et al.  Mammalian Vestibular Physiology , 1979, Springer US.

[35]  A. Stoppani,et al.  Structural requirements for steroid binding and quenching of albumin fluorescence in bovine plasma albumin. , 1976, Biochimica et biophysica acta.

[36]  A. Stoppani,et al.  Structural requirements for the action of steroids as quenchers of albumin fluorescence. , 1975, Biochimica et biophysica acta.

[37]  S. Folstein,et al.  “Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician , 1975 .

[38]  I. T. Draper THE ASSESSMENT OF APHASIA AND RELATED DISORDERS , 1973 .

[39]  A. Vermeulen,et al.  Capacity of the Testosterone-Binding Globulin in Human Plasma and Influence of Specific Binding of Testosterone on Its Metabolic Clearance Rate , 1969 .

[40]  R. Bulbrook,et al.  Metabolic clearance rates of pregnenolone, 17-acetoxypregnenolone and their sulphate esters in man and in rabbit. , 1967, The Journal of endocrinology.

[41]  R. Bulbrook,et al.  Binding of the sulphate esters of dehydroepiandrosterone, testosterone, 17-acetoxypregnenolone and pregnenolone in the plasma of man, rabbit and rat. , 1967, The Journal of endocrinology.

[42]  P. Rubé,et al.  L’examen Clinique en Psychologie , 1959 .

[43]  E Roberts,et al.  A systems approach to aging, Alzheimer's disease, and spinal cord regeneration. , 1990, Progress in brain research.

[44]  W. Regelson,et al.  The Biologic role of dehydroepiandrosterone (DHEA) , 1990 .

[45]  M. Gershengorn Mechanism of thyrotropin releasing hormone stimulation of pituitary hormone secretion. , 1986, Annual review of physiology.

[46]  H. Nordenstam,et al.  On the occurrence of phenol and steroid sulphokinases in the human gastrointestinal tract. , 1968, Scandinavian journal of gastroenterology.