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Biomedical subjects

L N Parker

Publications and source records attributed to L N Parker.

18 recordsLinked to original sources
PubMed1991

Control of adrenal androgen secretion.

The human adrenal gland secretes large amounts of androgens and androgenic precursors as compared with the adrenal glands of other species. In part, this pattern of secretion is regulated by ACTH, analogous to the control of cortisol. However, in many instances, including adrenarche, puberty, aging, and severe illness, secretion of adrenal androgens and cortisol diverge for reasons which are not clear. Factors endogenous to the adrenal gland may have a role in the modulation of adrenal androgen secretion. These include the centripetal blood supply of the adrenal gland, availability of cofactors of steroidogenic enzymes, and intrinsic properties of adrenal cells or enzymes. However, these mechanisms may, in turn, be modified by factors exogenous to the adrenal gland. Possible evidence for a regulatory role for such known substances as growth hormone, IGF-1, gonadotropins, estrogens, angiotensins, prostaglandins, insulin, EGF, and POMC-related peptides is discussed. Furthermore, pituitary or extrapituitary substances, in addition to known hormones, may have a role in the control of adrenal androgen secretion. Several lines of evidence include the inability of ACTH to maintain a normal adrenal androgen/cortisol ratio in adrenally suppressed patients, or experimentally, in hypophysectomized chimpanzees. Evidence for such factors derived from fetal and adult human pituitary gland is discussed.

Adrenal Glands↗
PubMed1991

Adrenarche.

Between 6 and 8 years of age, while cortisol concentrations and production rates remain constant, urinary excretion and circulating concentrations of DHA, DHAS, and other adrenal androgens increase progressively. These hormonal changes, which constitute the adrenarche, are accompanied by the appearance of axillary and pubic hair and a transient acceleration of linear growth and bone maturation. Increased adrenarchal concentrations of adrenal androgens may also contribute to the observed developmental decrease in concentration of SHBG and increase in bioavailable testosterone that occur in preadolescent boys. It is not known if extraadrenal factors, intraadrenal factors, or a combination of both are responsible for the occurrence of adrenarche. However, known hormones, such as ACTH, prolactin, gonadotropins, and estrogens, do not appear to cause the adrenarche. During adolescence, ACTH and cortisol concentrations remain constant, but concentrations of adrenal androgens continue to increase. The existence of a relationship between adrenarche and puberty has been suggested, partly because increased concentrations of adrenal androgens in undertreated congenital adrenal hyperplasia have been associated with cases of true precocious puberty in boys. However, there is evidence against a causal relationship, including the observation that children with treated primary adrenal insufficiency have been found to enter puberty normally. Adrenarche may cause a transient acceleration of growth and serve as a permissive factor in male puberty but does not appear to be necessary for the initiation of puberty.

Adrenal Cortex Hormones↗
PubMed1991

Malignant transformation of a Hürthle cell tumor: case report and survey of the literature.

Hürthle cell carcinoma is a relatively uncommon type of well-differentiated thyroid carcinoma. Its diagnosis has been controversial due to the difficulty in separating Hürthle cell adenoma from Hürthle cell carcinoma, thus the term Hürthle cell tumor is often used to describe both lesions. The present case of anaplastic giant-cell carcinoma in an 81-yr-old woman arose in a Hürthle cell tumor. This case illustrates the propensity of Hürthle cell tumor to undergo "malignant transformation" and argues for a more aggressive approach to such tumors.

Adenoma↗
PubMed1990

Induction of type II T4-5'-monodeiodinase activity in brown adipose tissue in fasted mice.

In order to study the effect of starvation on brown adipose tissue (BAT) type II 5'-monodeiodinating activity (5'MDI), type II 5'MDI was measured in vitro in the presence of 20 mM dithiothreitol, 1 mM propylthiouracil, 2 nM thyroxine (T4) and appropriate amounts of 600 X g infranatant of BAT from fed control or 3 day fasted mice, with or without daily T4 replacement (1.2 micrograms/100 g bw) during starvation. I- released from 125I-T4 was measured by ion-exchange column chromatography. Activity of BAT 5'MDI was markedly elevated in the 3 day fasted group (133 +/- 28 fmol I-/h per mg protein vs. 26 +/- 6.4; p less than 0.05). Kinetic studies using BAT infranatant suggested that fasting-induced activity is associated with a similar change in the Vmax, but no demonstrable change in apparent Km of T4 monodeiodination. T4 replacement during fasting, which normalized both serum T4 and T3 in fed and 3 day fasted groups, did not stop the increase of BAT 5'MDI in the fasted group (p less than 0.01). The data suggest that: (1) the fasting-induced increase in BAT 5'MDI is due mainly to the changes in capacity rather than the affinity of the enzyme, and (2) the fasting-induced increase in BAT 5'MDI is not mediated entirely through changes in serum thyroid hormone concentration.

Adipose Tissue↗
PubMed1990

Dehydroepiandrosterone reduces cancellous bone osteopenia in ovariectomized rats.

The effects of dehydroepiandrosterone (DHA) on cortical bone at the tibial diaphysis and cancellous bone at the tibial metaphysis were determined in intact and ovariectomized rats. Total plasma DHA was reduced at 10 and 16 wk after ovariectomy. Intact and ovariectomized rats were implanted monthly with controlled-release subcutaneous pellets containing 2.5 mg of DHA or placebo. Plasma DHA was elevated in DHA-treated intact rats and was near normal in hormone-treated ovariectomized rats. Ovariectomy resulted in severe cancellous bone osteopenia, which was reduced in DHA-treated animals. Cross-sectional and cortical areas were increased at the diaphysis in ovariectomized rats, and this was not altered by DHA treatment. Bone formation at the endosteal and periosteal surfaces of the tibial diaphysis was decreased 16 wk after ovariectomy, and DHA treatment appeared to antagonize these changes. We interpret these results as evidence that decreased peripheral DHA levels contribute to the skeletal changes in ovariectomized rats.

Animals↗
PubMed1985

A genetic component to the variation of dehydroepiandrosterone sulfate.

Previous studies have shown wide variation in the normal range of serum concentrations of adrenal androgens, including dehydroepiandrosterone (DHA), and DHA sulfate (DHAS). Much of this variability has been shown to be due to the marked variation of the concentrations of these hormones with age. In a search for other sources of this variation, we examined the distribution of DHAS levels in 178 individuals drawn from 26 families. DHAS was chosen because of its relatively high serum concentration, long half-life, and lack of pulsatile variation. As expected, we observed a large age effect, such that it accounted for 68% of the overall variability. In addition, however, when age was factored out by appropriate polynomial regression, there was a significant genetic component to the residual variation, with a heritability of 65%. Thus there appeared to be a significant genetic determination to DHAS serum levels. The results are in accord with previous studies suggesting a genetic component to the variation in testosterone and sex hormone globulin concentrations, and the known correlation of DHAS and testosterone levels. Thus there appears to be significant genetic control of androgen concentrations in humans.

Adolescent↗
PubMed1985

Evidence for adrenocortical adaptation to severe illness.

During serious illness, there are characteristic increases in serum cortisol concentrations and urinary cortisol excretion. In the present studies, we investigated these changes in glucocorticoid metabolism in relation to adrenal androgen metabolism, as measured by RIA of dehydroepiandrosterone (DHA) and DHA sulfate (DHAS). A group of 23 seriously ill men with various disorders, ill for a week or longer, was age-matched to a control group of 25 men, and the following changes were found: 1) basal serum cortisol concentrations were elevated in the ill group (P less than 0.001), 2) basal serum DHA and DHAS concentrations tended to be lower in the ill group (P less than 0.1); 3) basal serum DHA to cortisol and DHAS to cortisol ratios were decreased in the ill group by 80.3% and 77.2%, respectively (P less than 0.001); 4) ACTH-stimulated serum cortisol concentrations increased by the same absolute amount in both groups, whereas the increase in stimulated DHA concentrations in the ill group was 57.2% less (P less than 0.05), indicating a defect in ACTH-stimulated DHA reserve in serious illness; 5) basal daily unconjugated DHA excretion was lower in the ill group (P less than 0.05); (6) basal daily cortisol excretion was higher in the ill group (P less than 0.05); and 7) the basal daily urinary unconjugated DHA to cortisol ratio was 85.4% lower in the ill group (P less than 0.001). Recently, Zipser et al. described the entity of hyperreninemic hypoaldosteronism in the seriously ill. Their findings combined with our own indicate a relative shift in the metabolism of adrenal pregnenolone in serious illness away from mineralocorticoids and adrenal androgens and toward glucocorticoids. The cause of this change is unknown. We speculate that this shift of relative biochemical pathway predominance may be a factor necessary for survival during chronic severe stress.

Adaptation, Physiological↗
PubMed1985

Analysis of nonprescription capsules purported to contain an adrenal androgen.

The content of nonprescription capsules purported to contain dehydroepiandrosterone was analyzed. Five capsules labeled "dehydroepiandrosterone (DHEA) 500 mg and natural precursors" were analyzed; all were from a single lot and container. Ether extracts were used to test for DHEA, cortisol, testosterone, and androstenedione using radioimmunoassay (RIA). The protein, starch, reducing-sugar, sodium, potassium, calcium, and magnesium contents were also measured. The mean (+/- S.D.) DHEA content per capsule was 14.40 + 5.16 micrograms. A mean androstenedione concentration of 1.22 + 0.21 micrograms was measured. Cortisol and testosterone were not detectable by RIA. Concentrations of the other ingredients (mean +/- S.D. for five capsules) were as follows: protein 35.2 +/- 2.3 mg, starch 39.9 +/- 2.7 mg, reducing sugars 3.2 +/- 0.2 mg, sodium less than 1.5 mM, potassium less than 0.15 mM, magnesium 0.60 mg, and calcium 3.45 mg. The total amount of free DHEA contained in the capsules was only a small fraction of the labeled amount of that steroid and was probably inadequate for producing any measurable effects.

Capsules↗
PubMed1979

Evidence for existence of cortical androgen-stimulating hormone.

An animal model using dexamethosone-suppressed, castrated dogs was developed to test the hypothesis that a pituitary hormone other than ACTH modulates adrenal androgen (AA) secretion. Plasma samples were obtained every 15 min during infusions of saline, synthetic alpha 1-24 corticotropin, porcine 1-39 corticotropin (ACTH), or bovine pituitary gland extract (PE) in a wide range of doses. Androstenedione (A), dehydroepiandrosterone (DHA), and cortisol (F) were quantified by radioimmunoassay. When the ratio of AA levels was related to those of F, in order to correct for ACTH content in the PE, the slopes of the dose-response curves for corticotropin and PE were different at the 0.01 level. For A the dose-response slope for the PE was 0.18 +/- 0.5 SE, whereas that of ACTH was 0.02 +/- 0.01. For the DHA response the slopes were 0.17 +/- 0.04 for the PE and 0.04 +/- 0.03 for ACTH. Related studies showed no increase in AA levels in response to luteinizing hormone-releasing hormone, bovine growth hormone (GH), bovine prolactin, ovine thyroid-stimulating hormone (TSH), or synthetic aqueous arginine vasopressin (AVP). We conclude that a pituitary factor other than ACTH, prolactin, GH, luteinizing hormone, follicle-stimulating hormone, TSH, or AVP may be responsible for the observed increase in AA concentrations.

Adrenal Cortex↗
PubMed1978

Adrenal androgens in patients with chronic marked elevation of prolactin.

It has been postulated, based on data in animals and the fact that the cortisol-adrenal androgen ratio is different before and after adrenarche, that prolactin (Prl) may modulate adrenal androgen secretion. As one way of testing this hypothesis, cortisol, androstenedione (A), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were measured by radioimmunoassay in the sera of thirteen patients with suspected or proven pituitary tumours and marked chronic elevations of serum Prl (range 68-990 ng/ml, mean 198.9 ng/ml). Values for cortisol, A, DHA, and DHAS were not significantly different between the groups of normal controls and patients with elevated Prl concentrations. This is interpreted as negative evidence for the theoretical connection between Prl and adrenal androgen secretion.

Androstenedione↗
PubMed1978

Decline of adrenal androgen production as measured by radioimmunoassay of urinary unconjugated dehyroepiandrosterone.

Dehydroepiandrosterone (DHA), in large part a measure of adrenal androgen secretion, previously has been measured in urine after hydrolysis or solvolysis of the glucuronide and sulfate conjugates. These procedures are time consuming; they often require several days and variable recoveries are a source of error. A method is presented here for determination of unconjugated DHA in 24-h urine specimens which requires less time, labor, and sample volume than necessary for the assay of DHA derived from conjugates. In 76 men and women, age 20-96 yr, total 24-h urinary unconjugated DHA showed no sex differences. However, the mean unconjugated DHA excretion decreased, which may indicate decreased zona reticularis function with respect to relatively constant zona fasiculata function in advancing age.

Adrenal Glands↗
PubMed1977

An improved radioimmunoassay for 4-androstene-3,17-dione.

A radioimmunoassay using an antiserum produced against 6beta-hydroxy-4-androstene-3,17-dione-6-succinyl-BSA conjugate is described which permits the rapid determination of 4-androstene-3,17-dione in multiple serum samples that are purified by column chromatography on neutral alumina. Steroids which reacted significantly with the antiserum were found to be 5alpha-androstane-3,17-dione, 5beta-androstane-3,17-dione, and 6beta-hydroxy-4-androstene-3,17-dione. After column chromatography on alumina, however, the only significantly cross-reacting steroids were the 5alpha and 5beta-androstane-3,17-diones, while cross-reactivity from other steroids was reduced to less than 1%.

Adult↗
PubMed1976

Treatment of obesity by acupuncture.

Twenty-four subjects ranging from 5 to 33% above ideal weight were weighted during a 3-week control period, and then treated for the successive 9 weeks with acupuncture therapy given in three different loci, and in random order for 3-week periods. The acupuncture needles were placed in unilateral loci used by oriental acupuncturists for weight loss, in the same loci bilaterally, and in unilateral loci not used by acupuncturists for weight loss. No undesirable effects were noted. No treatment was associated with weight reduction significant at the 0.05 confidence level. A study involving guinea pigs was run parallel with the above clinical protocol and also demonstrated no effect of ear acupuncture on weight loss.

Acupuncture Therapy↗
PubMed1975

Some aspects of brain neurochemistry after intrauterine exposure to tritium.

Rats were continuously exposed to tritiated water (0, 1, 10 and 100 muCi HTO/ml body water) from conception to birth. Calculated, cumulative whole-body doses to the embryo and foetus were approximately 0, 6-6, 66 and 660 rad. The levels of several enzymes and established or presumptive central nervous system neurotransmitters were examined postnatally in whole brains. These were norepinephrine (NE), dopamine (DA), acetylcholinesterase (AChE) and monoamine oxidase (MAO). Intrauterine exposures to doses as low as 66 rad produced measurable and persistent decreases in brain weight and increases in NE concentrations at 21 and 45 days postnatally. No differences from control values were seen in the rate of turnover of NE or the concentrations of DA, AChE or MAO at 45 days. Exposure in utero to 6-6 rad produced no detectable postnatal effects on the brain neurochemical parameters measured.

Acetylcholinesterase↗