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J F Nelson

Publications and source records attributed to J F Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1988

Puberty, gonadal steroids and fertility: potential reproductive markers of aging.

Three potential predictors (i.e., biomarkers) of longevity in mammals are proposed: (1) age of pubertal onset, (2) concentrations of gonadal steroids and (3) timing of age-related infertility. Ages of pubertal onset and of declining fertility are hypothesized to be positively correlated with longevity. Concentrations of and androgens and estrogens are proposed to be inversely and positively correlated, respectively, with life span. Evidence upon which these hypotheses are based is reviewed and its limitations are discussed. General strategies for testing these hypotheses are outlined. In addition, several pragmatic as well as theoretical issues facing research on biomarkers of aging are discussed, using specific examples derived from studies of female reproductive aging.

Aging↗
PubMed1988

Aging and chronic estradiol exposure impair estradiol-induced cornification but not proliferation of vaginal epithelium in C57BL/6J mice.

Long-term exposure of adult female rodents to estrogen has many deleterious effects on reproductive neuro-endocrine structure and function, but its effects on peripheral target tissues are not well known. This study was designed to determine whether chronic exposure of young mice to estradiol (E2) alters the response of the vagina to E2, and if so, whether aging potentiates this alteration. Eight-week-old mice were ovariectomized (ovx) and given subcutaneous Silastic or polyethylene (PE) implants containing E2. Silastic implants produced supra-physiologic E2 levels, while E2 levels in PE-implanted mice were within the physiologic range. Initially all E2-exposed mice showed vaginal cornification (CORN). However, CORN soon began to decline and was virtually absent 3-5 mo after implantation, despite evidence of continued, albeit reduced, release of E2 from the implants. Mice were reimplanted with new E2 implants to determine whether the loss of CORN resulted from an altered response to E2 or from a decreased release of E2 from the implants. Vaginas of mice previously exposed to either Silastic (high E2) or PE (low E2) implants failed to cornify in response to new E2 implants, whereas vaginas of mice that had been initially exposed to implants without E2 cornified in response to identical E2 implants. When old (23 mo) acutely ovx mice were given E2-containing Silastic implants, the peak level and duration of CORN were only one-third and one-fifth, respectively, of that seen in young mice. Non-cornifying epithelia from both young and old chronically E2-exposed mice were as hyperplastic and active mitotically as cornifying epithelia, indicating that the loss of CORN was not a result of decreased epithelial proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Age-related changes in proopiomelanocortin messenger ribonucleic acid levels in hypothalamus and pituitary of female C57BL/6J mice.

Concentrations of POMC-derived neuropeptides are reduced in hypothalami of aged rodents, whereas levels of POMC products in the pituitary are usually either unchanged or increased. Whether these changes reflect altered synthesis or processing of POMC or altered expression of the POMC gene has not been established. We, therefore, measured POMC mRNA in hypothalami and pituitaries of young (7-month-old), middle-aged (15-month-old), and old (31-month-old) female mice, using slot blot hybridization of total RNA to riboprobes synthesized from cloned POMC DNA fragments. Concentrations of poly(A) and ribosomal RNA were also determined, using probes synthesized from poly(T) and a cloned ribosomal DNA fragment, respectively. Hypothalamic POMC mRNA content and concentration were 30% lower in old than in young and middle-aged mice (P less than 0.01). This change was not due to a general decline in hypothalamic mRNA or rRNA levels, neither of which changed with age. In contrast to the hypothalamus, the relative concentration of POMC mRNA in the pituitary nearly doubled in old mice (P less than 0.01). This increase was secondary to a decrease in other RNA species, however, since the total pituitary content of POMC mRNA did not differ between young and old mice. These results indicate that the regulation of POMC gene expression during aging differs in hypothalamus and pituitary, and that reduced levels of hypothalamic POMC mRNA may account for the previously reported reductions in concentrations of hypothalamic POMC peptides during aging.

Aging↗
PubMed1987

Aging of the hypothalamo-pituitary-ovarian axis: hormonal influences and cellular mechanisms.

Longitudinal studies employing heterochronic ovarian grafts and long-term ovariectomy indicate that there is no single pacemaker of reproductive aging. Neuroendocrine dysfunction, the declining follicular reserve, and ovarian secretions all contribute to reproductive decline, and their relative importance to the different stages of reproductive aging varies markedly. Moreover, although ovarian secretions during adulthood potentiate certain aspects of the reproductive aging process, their behavior does not fit a simple model of cumulative steroidal damage incurred over the lifespan. Current data are more consistent with temporally distinct windows of steroidal vulnerability for the events affected: cycle lengthening is affected by ovarian secretions during the period of cyclicity, and post-cyclic neuroendocrine failure is potentiated by ovarian secretions during the peri- and post-cyclic period of the lifespan. Recent examination of estradiol receptor dynamics reveals multiple, albeit selective, changes during aging that may contribute to the age-related impairments of tissue sensitivity to estrogen. These changes vary qualitatively and quantitatively among target tissues. Thus, aging of the hypothalamo-pituitary-ovarian axis at the cellular level mirrors, in its multifactorial nature, aging at the organismic level.

Aging↗
PubMed1987

Changes in sodium appetite in cattle induced by changes in CSF sodium concentration and osmolality.

Alteration of the sodium concentration in the cerebrospinal fluid (CSF) of sheep induces reciprocal changes in sodium appetite. Similar studies have now been performed in cattle. Heifers were prepared with a unilateral parotid fistula and guide tubes were implanted in the skull for the introduction of probes into the lateral ventricles in order to sample CSF and infuse artificial CSF solutions. The cows were Na depleted by loss of saliva for 46 hr and then given free access for 2 hr to 300 mM NaCl/NaHCO3 solution. Artificial CSF infusions at 1.9 ml/hr were begun one hour before Na access. In control experiments, the cows drank 26.4 +/- 1.2 l of Na solution in 2 hr, 1.2 +/- 0.2 l of water in the preceding hour, and 0.3 +/- 0.1 l of water during Na access. Sham or standard isotonic CSF infusions did not alter these values. CSF [Na+] rose from approximately 142 to approximately 148 mmol/l, attributable to the effects of drinking the large volume of hypertonic Na solution. Infusion of 500 mM NaCl CSF increased CSF [Na+] and reduced Na intake and increased water intake. Infusion of 700 mM mannitol: 150 mM NaCl CSF reduced CSF [Na+] and increased both Na and water intake. Infusion of a mixture of these solutions had no effect on CSF [Na+] and increased water intake only. Infusion of 270 mM mannitol CSF reduced CSF [Na+] and slightly reduced Na intake. Standard isotonic CSF containing 0.5 or 2.0 micrograms/ml of angiotensin II increased water intake only.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1987

Tissue differences in estrogen receptor dynamics: nuclear retention, rate of replenishment, and transient receptor loss vary in hypothalamus, pituitary, and uterus of C57BL/6J mice.

Little is known about tissue differences in estrogen receptor (ER) dynamics, despite evidence that they could play a role in the tissue specificity of estrogen action. This study was designed to test the hypothesis that ER dynamics differ in uterus (UT), pituitary (PIT), and hypothalamus (HYPO), as measured by 1) duration of peak nuclear ER (ERn), 2) rate of replenishment of cytosolic ER (ERc), and 3) loss of total ER (ERt) after a bolus of estradiol (E2). Young adult mice were studied at two hormonally distinct stages of the cycle [days 2 or 3 (D2-3) and D5 (D1 = proestrus)]. Animals were injected with a dose of E2 (0.05 microgram/10 g BW) sufficient to achieve maximal ERn or with vehicle only, and ER was determined in nuclear and cytosolic fractions 1, 2, 4, 8, 12, and 24 h later. ERn peaked concomitantly with plasma E2 at 1 h in all tissues, but the duration of peak ERn varied among tissues: 4 h in HYPO compared to 1-2 h in UT and PIT. ERc replenishment was complete by 12 h in HYPO, but not until 24 h or more in PIT; replenishment in UT was intermediate (12-24 h). The transient loss of ERt after E2 injection was pronounced in UT and PIT, but was undetectable in HYPO. These tissue differences were maintained across cycle state, despite effects of cycle state on ER dynamics. The effects of cycle state on ER dynamics were also tissue specific; they were greatest in UT and absent in HYPO. On D2-3 in UT, ERn and ERt were lower, and replenishment of ERc was slower than on D5. Parallel effects of cycle state were seen in PIT, with the exception of ERn, which was unaffected. Because altered ER dynamics similar to those observed on D2-3 can be produced by progesterone pretreatment, the altered ER dynamics on D2-3 may be a consequence of recent exposure on D1 to the ovulatory surge of progesterone. Taken together, these results indicate that the mechanisms governing intracellular ER dynamics vary markedly among tissues and provide an impetus for further examination of their role in the tissue specificity of estrogen action.

Animals↗
PubMed1987

Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion.

Although the menopause is generally considered to be the consequence of follicular exhaustion, the relationship between follicle number and the menopausal transition has not been explicity studied. We addressed this question in 17 women, aged 45-55 yr, who were undergoing elective total abdominal hysterectomy and salpingo-oophorectomy. The women were divided into 3 groups according to their menstrual history: 1) menstruating regularly (n = 6), 2) perimenopausal (irregular menses; n = 7), and 3) postmenopausal (greater than 1 yr since last menses; n = 4). The mean ages of the 3 groups were similar. Menstrual histories were confirmed by plasma hormone levels and endometrial histology. One ovary from each woman was serially sectioned for determination of follicle numbers. The mean number of primordial follicles in the ovaries of women who were still menstruating regularly was 10-fold higher than that in perimenopausal women [1392 +/- 355 (+/- SEM) vs. 142 +/- 72]. Follicles were virtually absent in the postmenopausal ovaries. Comparison of these data with those obtained by others in younger women suggests that follicular depletion accelerates dramatically in the last decade of menstrual life. These results support the view that declining follicular reserve is the immediate cause of both the perimenopausal and menopausal transitions, and indicate that the rate and, therefore, the regulation of follicular depletion change during the final phase of reproductive life.

Endometrium↗
PubMed1987

Extramedullary plasmacytoma of the thyroid.

We report a patient with solitary extramedullary plasmacytoma of the thyroid gland. We describe the computed tomographic findings correlated with the radionuclide imaging and surgical findings and review the related literature.

Humans↗
PubMed1986

Prolongation and cessation of estrous cycles in aging C57BL/6J mice are differentially regulated events.

The relative contributions of ovarian failure and hypothalamic-pituitary dysfunction to the prolongation and cessation of estrous cycles were assessed by measuring the ability of acutely ovariectomized (OVX) middle-aged (12 mo) mice to cycle after receiving grafts (under the renal capsule) of ovaries from young (2 mo) mice. The potentially disruptive effect of the acyclic state on the cycling response to grafted, young ovaries was avoided restricting grafting to middle-aged hosts that were still cycling. The effect of chronic exposure to ovarian secretions before the cessation of cyclicity on age-related hypothalamic-pituitary dysfunction was also assessed. The cycling ability of long-term OVX middle-aged mice (i.e., OVX at 3 mo) bearing grafts of young ovaries was compared to that of age-matched acutely OVX controls. Grafted young ovaries extended the cycling lifespan of acutely OVX middle-aged hosts by 60%. The length of this extended cycling lifespan, however, was only 80% of that achieved by young hosts bearing grafts of young ovaries. Young ovaries in middle-aged mice markedly lowered the incidence of long cycles (greater than 5 days), shifting the modal cycle length to 5 days. However, young ovaries in middle-aged mice failed to increase the incidence of 4-day cycles, the modal cycle of young controls. Middle-aged ovaries grafted into young hosts lengthened their cycles and shortened their cycling lifespan to middle-aged values. Long-term ovariectomy failed to increase the cycling lifespan of middle-aged hosts bearing grafts of young ovaries beyond that achieved in acutely OVX mice. Long-term ovariectomy did shorten the modal cycle length of middle-aged mice to 4 days, although the duration of 4-day cycling was only one-third (2 mo) that of young controls. These results indicate that the relative contributions of ovarian and neuroendocrine factors to three major events of reproductive aging vary with each event. Whereas the hypothalamic-pituitary unit appears to play an important role in the initial shift from 4- to 5-day cycles, the aging ovary plays the major role in the subsequent shift to longer cycles and in the ultimate cessation of cyclicity. Although chronic exposure to ovarian secretions during the period of cyclicity does not play a major role in the cessation of cyclicity, it appears to contribute to the hypothalamic-pituitary changes responsible for the initial shift from 4- to 5-day cycles.

Aging↗
PubMed1986

Radical ovarian resection advances the onset of persistent vaginal cornification but only transiently disrupts hypothalamic-pituitary regulation of cyclicity in C57BL/6J mice.

In aging laboratory rodents, neuroendocrine failure to support estrous cyclicity is in part the consequence of exposure to ovarian secretions during adulthood. Moreover, some evidence suggests that those secretions associated with the predominant postcyclic state, persistent vaginal cornification (PVC), are more deleterious than those associated with cyclicity. However, it is not clear whether postcyclic hormonal secretions are intrinsically more deleterious or whether vulnerability to ovarian secretions, regardless of their nature, increases during aging. Using relatively young, age-matched mice, this study was designed to control for age and to determine if the hormonal milieu associated with PVC would be more deleterious to neuroendocrine function than that associated with regular cyclicity. Onset of PVC was advanced about 5 mo by resecting 90-95% of the ovarian tissue from 5-mo-old mice. The resultant PVC was similar in duration, vaginal cytology and ovarian histology to that seen in normally aging mice. At age 13 mo, when mean duration of PVC was 3 mo in resected mice but only 1 mo in sham-operated controls, the ability of mice to support cyclicity upon receipt of ovarian grafts from 4-mo-old donors was tested as an index of neuroendocrine function. The response of resected mice was slightly impaired, but only during the first month after grafting. This transient disruption of neuroendocrine function in mice prematurely exposed to PVC stands in contrast to the irreversible loss of cycling potential in older animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Effects of ouabain, amiloride, monensin, and other agents on ovine parotid secretion.

Secretion by the parotid gland of Na-replete and -depleted sheep was investigated by examining the effects of modifiers of ionic transfer on salivary composition and flow rate. These agents were infused into the arterial blood supply of the vascularly isolated gland in anesthetized sheep. Ouabain inhibited Na+-K+ exchange in the ducts caused by Na depletion and restored the [Na+], [K+], and osmolality to close to those of Na-replete saliva. Ouabain also inhibited Cl- -HCO3- exchange in the ducts in Na repletion and depletion. Amiloride partially inhibited Na+-K+ exchange in Na depletion without affecting Cl- -HCO3- exchange. Monensin potentiated Na+-K+ exchange in Na repletion and depletion. Amiloride and monensin gained access to the saliva, but furosemide and ethacrynic acid were almost totally excluded, and, up to 10(-3) M in blood, they did not affect salivary composition or flow rate. Methazolamide gained free access to saliva but was without effect. 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid at 10(-3) M slightly increased salivary [Na+] and [HPO4(2-)]. The results indicate potent effects of ouabain on basolateral Na+-K+ pumps and of amiloride and monensin on transcellular delivery of Na+ to these pumps, but ouabain had no effect on salivary flow rate until O2 consumption approached zero and secretion failed. The findings do not support a proposal that the salivary secretion depends on a Cl- -dependent furosemide-sensitive system energized by Na+-K+-ATPase-dependent Na pumps.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1985

Dehydration-induced sodium appetite in rats.

The effect of 24 hr water deprivation on Na balance was studied in rats. Under baseline conditions, the animals had free access to food and water. During water deprivation, Na excretion was increased, Na intake (i.e., food intake) was decreased and Na deficits of 0.8-1.0 mmol were incurred. During the 24 hr period immediately following the deprivation period when water was returned, Na excretion was decreased and Na balance was restored to baseline or pre-deprivation level. In a second series of experiments, under baseline conditions, the animals had free access to food, water and 0.5 M NaCl. During water deprivation with NaCl solution withheld, Na excretion was not changed relative to baseline but Na deficits of 0.8-1.0 mmol were incurred due to decreased Na intake. During the 24 hr period immediately following deprivation when both water and NaCl solution were returned, intake of the hypertonic NaCl solution was increased and Na balance was restored. In a third series of experiments, under baseline conditions, the animals had free access to food, water, 0.5 M NaCl, 0.5 M KCl, 0.25 M of MgCl2 and 0.25 M CaCl2. During the 24 hr period following water deprivation and also the withholding of the electrolyte solutions, the appetite induced was predominantly for NaCl. The results suggest that the Na appetite observed subsequent to a period of water deprivation may be due to Na deficiency.

Animals↗
PubMed1985

The voluntary correction of sodium deficiency by the rabbit.

The behaviour involved in the correction of sodium deficit has been studied in wild rabbits and also laboratory bred rabbits. They were offered 0.5 M NaCl to drink. In adrenalectomized wild rabbits variable sodium deficits were produced by withdrawal of mineralocorticoid for 24-72 hr. Correction of the deficit was remarkably precise and was achieved in 9-24 hr, being slower with smaller deficits. That is, the rate of drinking was almost commensurate with the degree of body deficit. No overdrinking occurred by 24 hr. Repetition of the experiment with 24 hr deficiency and with the offer of a cafeteria of 0.5 M NaCl, 0.5 M KCl, 0.25 M CaCl2 and 0.25 M MgCl2 showed the increased appetite was specific for NaCl. Both wild and laboratory rabbits, adrenally intact, were made sodium deficient by the diuretic furosemide. Voluntary salt intake did not peak until 6-12 hr later reflecting the characteristic delay in the genesis of salt appetite. If presentation of salt were delayed 24 hr after furosemide, the highest rate of intake was seen immediately in both wild and laboratory rabbits, but the wild rabbits were much faster in fully correcting body deficit. Infusion of isotonic NaCl, adequate to correct the deficit, given during the third-sixth hour of access to NaCl under the 24 hr delay of presentation regime, halved salt appetite over this period, and by 9-12 hr it was abolished. Polyethylene glycol induced subcutaneous fluid sequestration, salt appetite and thirst but caused an obvious severe deterioration in the animals condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1985

Effect of dietary restriction on estrous cyclicity and follicular reserves in aging C57BL/6J mice.

Restricting the food intake of female mice by alternating days of feeding and fasting delayed the age-related loss of estrous cycling potential and retarded the rate of follicular depletion, as determined after reinstatement of ad libitum (AL) feeding. During the period of food restriction (FR; 3.5-10.5 mo), food intake and body weight were about 80% of AL values. Mice were acyclic and predominantly in a state of diestrus during FR, but after reinstatement of an AL diet at 10.5 mo all FR mice resumed cycling regularly. By contrast, 80% of AL controls had become acyclic by this age, and the cycles of the remaining mice were significantly longer than those of the reinstated FR mice. Follicular reserves of 12.5-mo-old FR mice were twice those of age-matched AL controls. Cycling performance of reinstated FR mice, measured by cycle length and the proportion of mice still cycling, was equivalent to that of AL mice when the latter were 2-5 mo younger. Ovarian age, measured by the size of the follicular reserve, was similarly retarded in FR mice. Based on these data and previous evidence that follicular depletion plays a major role in the cessation of cyclicity in this strain, we hypothesize that the delayed loss of estrous cyclicity in aging FR mice is mediated at least in part by the retarding effect of dietary restriction on the rate of follicular depletion.

Aging↗
PubMed1985

Water and salt intake of wild rabbits (Oryctolagus cuniculus (L)) following dipsogenic stimuli.

Wild rabbits trapped in their natural habitat and adapted to laboratory conditions were studied. Food, water and electrolyte (0.5 M-NaCl, 0.5 M-KCl, 0.25 M-MgCl2 and 0.25 M-CaCl2) consumption, urinary volume and sodium losses were monitored daily following stimuli which were found dipsogenic in other species. Water drinking was observed immediately after the intravenous injection of 1 M-NaCl (3 ml/kg), and following withdrawal of a mean of 13.9% of calculated blood volume. Daily intake of water decreased during intracerebroventricular (I.C.V.) infusion of 0.3 M-NaCl in artificial cerebrospinal fluid (c.s.f.), during I.C.V. infusion of 0.9 M-mannitol c.s.f., both at a rate of 17 microliters/h, following peritoneal dialysis with 5% (w/v) glucose solution, and during food restriction. Water intake was not affected following intravenous administration of acetazolamide (10 mg/kg). Daily intake of 0.5 M-NaCl solution was increased following peritoneal dialysis with 5% (w/v) glucose solution, which caused hyponatraemia, but not after haemorrhage which caused about the same sodium deficit as peritoneal dialysis, but as an isosmotic loss. Administration of two different angiotensin II analogues, systemically or I.C.V., failed to induce water drinking. However, urinary sodium excretion and intake of 0.5 M-NaCl were increased during the 5 days of I.C.V. infusion of angiotensin II (10 pmol/h). Infusion for 1 day of angiotensin II (500 pmol/h) led to increased urinary sodium excretion which was followed by increased intake. The intake of other electrolyte solutions was not significantly affected by any of the treatments detailed above. The mechanisms participating in initiation of thirst in wild rabbits are very sensitive to decrease in blood volume, in contrast to other species studied in laboratories. Angiotensin II at the doses and routes administered was not dipsogenic in wild rabbits. The increased intake of 0.5 M-NaCl solution observed during and after the long-term intraventricular administration of angiotensin II in the wild rabbit appears predominantly a response to sodium deficit caused by natriuresis. The persistence of appetite after the cessation of infusion is indicative of a residual effect on central mechanisms of salt appetite.

Acetazolamide↗