Richard F Walker

University of South Florida | USF · Biological Sciences

Senescence violates the most basic tenet of natural selection by causing death rather than individual survival. Thus, current theories favor the concept of antagonistic pleiotropy (AP) to explain how aging emerged in metazoans. Presumably, pleiotropic genes reduce vigor and limit longevity in adults. However, they also promote fitness and reproduct...

In 1932, Bidder postulated that senescence results from "continued action of a (genetic) regulator (of development) after growth ceases (maturation occurs)." A 16-year-old girl who physically appears to be an infant has not been diagnosed with any known genetic syndrome or chromosomal abnormality. The subject's anthropometric measurements are that...

Richard F WalkerInternational Society for Applied Research in Aging (SARA)There is consensus among practitioners of age-management/longevity medicine that progressive failure of neuroendocrine function leads to hormone insufficiency, which underlies many of the maladaptive consequences of aging. Accordingly, one of the most commonly employed clinic...

Richard F WalkerInternational Society for Applied Research in Aging (SARA)The Society for Applied Research in Aging (SARA) was founded to serve the needs of practitioners who seek to sustain health, vitality, and quality of life of their patients during aging. Recognizing that a most basic and important part of that task is to provide relevant prof...

The concepts of "anti-aging" and "anti-aging medicine" in particular are hotly debated now, both in the mass media and among some researchers. This paper represents an open discussion of anti-aging terms and related ideas by nine leading experts in the field of aging studies, and it describes in detail the arguments presented by both supporters and...

The concepts of "anti-aging" and "anti-aging medicine" in particular are hotly debated now, both in the mass media and among some researchers. This paper represents an open discussion of anti-aging terms and related ideas by nine leading experts in the field of aging studies, and it describes in detail the arguments presented by both supporters and...

Empirical and scientific evidence suggest that functional deterioration of tissues and organs during aging is causally related, at least in part to decrements in anabolic hormones and/or their activities. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are examples of potent anabolic hormones with ubiquitous effects. Their circulating...

This study was conducted primarily to determine the utility of recombinant growth hormone releasing hormone (GHRH) and xenobiotic GH-releasing peptide (GHRP) administered sequentially or in combination, as diagnostic agents for pituitary-based, GH secretory dysfunction in aging men. The secondary purpose was to test the hypothesis that loss of sens...

Historical Perspective: A novel group of orally active peptide and nonpeptide growth hormone (GH) secretagogues have significant potential for treatment of short stature, aging, hyperprolactinemia, and prolactinomas. In this manuscript, the experimental evidence providing the basis for postulating an endogenous ligand for growth hormone-releasing p...

We have devised a diagnostic test to directly evaluate pituitary secretory potential, and also to identify the most appropriate therapy for slow growing children. The test compares responses to GH releasing hormone (GHRH) and GH releasing peptides or their non-peptidyl mimics (GHRP) administered sequentially and in combination. Since they are funct...

There is a progressive decrease in growth hormone (GH) secretion during aging that could result from several factors. Two of the most obvious are inadequate stimulation of the pituitary gland by hypothalamic hypophysiotropic factors, and/or degeneration of pituitary-based mechanisms for GH production/secretion. Of the two, it is most likely that de...

The decision to develop a drug for commercial application after its discovery is dependent upon preclinical information derived from studies in animal models. In vitro tests are generally the first screen used to evaluate various aspects of efficacy. Primary cell cultures or tumor cell lines and membrane preparations are generally employed as prima...

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita­ tive change in GH secretion was the net result of pituitary stimula...

The definitive diagnosis of growth hormone (GH) deficiency and the predetermined identification of short-statured children treatable with GH remain enigmas. The purpose of this chapter is to briefly summarize the physiology of GH secretion and relevant pharmacologic data as they relate to GH treatment. Last, some ethical issues regarding GH treatme...

Growth hormone (GH) secretion declines during aging. Since GH alters plasma cholesterol (PC) concentrations, it was of interest to determine how GH secretagogues affect age-related hypercholesterolemia. Fischer 344 rats (3 and 14 months old) were co-administered (s.c.) GH releasing hormone (3 micrograms/kg; GHRH) and GH releasing hexapeptide (100 m...

Degenerative changes in body composition characterized by reduced muscle and bone mass decrease physical performance in the elderly. These decremental somatic changes correlate with reduced serum growth hormone (GH) concentrations. Limited availability of cadaver-derived hormone before the advent of recombinant gene technology precluded testing the...

This book is a compendium of proceedings from the Symposium on Growth Hormone II: Basic and Clinical Aspects. The intent of the sym­ posium was to review current aspects of the rapidly expanding science of growth hormone (GH) neuroendocrinology, especially those develop­ ments that occurred since our last meeting in 1985. The meeting was timely sin...

Growth hormona (GH) secretory responses to provocative stimulation tests are often blunted in short statured children. The objective of the present study was to evaluate various pituitary factors that may contribute to low GH secretion using rodent models that are hyporesponaive to GH secretagogues. Plasma GH concentrations did not increase above b...

The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergi...

The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergi...

The purpose of this study was to evaluate the contribution of endogenous GH-releasing hormone (GHRH) to exogenous GH-releasing hexapeptide (GHRP-6) activity, and to determine whether TRH or GnRH are endogenous analogs of GHRP-6. The activity of GHRP-6, a synthetic GH secretagogue, was significantly attenuated in rats administered GHRH antiserum or...

The purpose of this study was to evaluate the contribution of endogenous GH-releasing hormone (GHRH) to exogenous GH-releasing hexapeptide (GHRP-6) activity, and to determine whether TRH or GnRH are endogenous analogs of GHRP-6. The activity of GHRP-6, a synthetic GH secretagogue, was significantly attenuated in rats administered GHRH antiserum or...

This series of experiments was conducted to evaluate the growth hormone (GH) releasing activity of intranasally administered His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6, SK&F 110679) in conscious dogs. Intranasal administration of GHRP-6 increased plasma growth hormone levels in the conscious dog in a dose-related manner. Doses of 0.25 and 0.5 mg/kg pr...

The purpose of this study was to compare GH secretion after the administration of GH-releasing hexapeptide (GHRP-6) in conscious male and female rats. Plasma GH was significantly elevated in female rats (six of six) compared to male rats (three of six) 15 min after administration of a single sc injection of GHRP-6 (0.5 mg/kg). In male rats, GHRP-6...

Aging is associated with a blunted growth hormone (GH) secretory response to GH-releasing hormone (GHRH), in vivo. The objective of the present study was to assess the effects of aging on the GH secretory response to GH-releasing hexapeptide (GHRP-6), a synthetic GH secretagogue. GHRP-6 (30 micrograms/kg) was administered alone or in combination wi...

The purpose of this study was to evaluate the growth hormone (GH) releasing activity of orally administered His-D-Trp-Ala-D-Phe-Lys-NH2 (GHRP-6, SK&F 110679) in rats, dogs and monkeys. Rats were administered GHRP-6 orally by gavage or parenterally through femoral artery catheters. Blood was collected before and after GHRP-6 administration for estim...

GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-LysNH2; SK&F 110679) is a hexapeptide that specifically releases growth hormone. Although derived from methionine enkephalin, 3H-SK&F 110679 binding profiles suggest that it retains little mu or delta opioid activity. In the present study, dynorphin A was a potent inhibitor of SK&F 110679 binding. However, detailed s...

Analogues of the highly potent and delta-receptor-selective enkephalins 1-4 were prepared with alpha-amino-beta-mercapto-beta,beta-pentamethylenepropionic acid (Apmp) replacing the beta,beta-dimethylcysteine (Pen) at positions 2 or 5. The peptides 5-8 were prepared by employing D,L-Apmp and, following oxidative cyclization, the resulting diastereom...

The purpose of this study was to determine whether a 30-day administration of SK&F 86002-A2, an inhibitor of cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism, adversely affected reproductive cycles, ovarian structure, and/or pituitary/ovarian hormone secretion. Cyclooxygenase and 5-lipoxygenase enzymes catalyze the reactions le...

In a preliminary 30-day study, oral administration of SK&F 86002-A2, an inhibitor of prostaglandin and leukotriene synthesis, blocked ovulation and altered ovarian structure and hormone production in rats. The purpose of the present study was to determine if the locus of action of SK&F 86002-A2 for these effects was the ovary or some other site in...

As part of preclinical safety testing for carcinogenicity, postpubertal (50 days old) rats were dosed (0, 30, 90 or 180 mg/kg/day) with ibopamine (N-methyldopamine, 0,0'-diisobutyroyl ester.HCl; SK&F 100168) for 730 consecutive days. Neoplastic and nonneoplastic lesions were identified histologically in all rats that died during the period of dosin...

The pharmacodynamics of serotonin (5-hydroxytryptamine; 5-HT) uptake and release were studied in rat pineal glands. Initially, uptake was tested by incubating pineals with several concentrations of [ ³ H]5-HT. The incubation media also contained [ ¹⁴ C]mannitol to which cells are impermeable. Since [ ¹⁴ C]mannitol accumulates only in extracellular...

This study describes various elements of the mechanism controlling norepinephrine (NE)-mediated release of serotonin (5HT) from rat pineal glands. After radiolabelling the endogenous pool of pineal 5HT with 3H-5HT, individual pineal glands were exposed to depolarizing buffers or those containing NE. Although 3H-5HT was not released by 50mM potassiu...

Since pain and depression are influenced by opioids and antidepressants, it was of interest to explore their interaction with common CNS receptors. A method for binding site selectivity was used to evaluate antidepressant specificities in inhibiting mu versus delta opioid binding. With the very specific opioid probes used, DAGO and DPDPE, a wide ra...

Monoamine neuroleptics alter rodent responses to immunization, suggesting that norepinephrine (NE) and serotonin (5HT) are neuroimmunomodulatory in these animals. Although endocrine factors participate in their mechanism(s) of action, recent studies suggest that NE and 5HT also interact more directly with immunocompetent cells. This review provides...

Serotonin (5-HT) uptake into platelets from psychiatric patients and controls was measured in the morning and afternoon. Uptake varied with time of day in both groups studied, resulting in four recognizable patterns. Two patterns occurred in the majority of controls. In contrast, uptake patterns in the psychiatric patients were more variable, with...

The purpose of this study was to determine if serotonin (5-HT) is secreted by the pineal gland and also to define the parameters of its secretion. After radiolabelling the endogenous 5-HT pool, individual pineal glands were placed within perifusion chambers and stimulated with norepinephrine (NE). [3H]5-HT was rapidly released within 1 min of stimu...

The effect of continuous environmental illumination on thyroid gland activity was investigated as a function of development in larval bullfrogs, Rana catesbeiana. After exposure of premetamorphic and prometamorphic tadpoles to continuous light or darkness, thyroid activity was determined by measurement of total glandular accumulation and percent in...

The effects of chronic and acute cold temperature exposure on thyroid function were investigated in groups of adult lizards, Sceloporus cyanogenys. Some animals were placed in constant temperature chambers at 16°C for 2 wk prior to testing, while those exposed to acute cold were placed in a 4°C environment for 0.5 hr preceded by a 14-day acclimatio...

1.1. Estrogen treatment caused subtracheal fat body depletion with dramatic increases in free fatty acid concentrations in the lizard, Dipsosaurusdorsalis.2.2. Thyroid activity increased when free fatty acids were intramuscularly injected into experimental animals.3.3. Circulating free fatty acids may competitively inhibit thyroxine binding to seru...