Biomedical subjects

H Raff

Publications and source records attributed to H Raff.

At least 19 recordsLinked to original sources

PubMed2006

An oxidized derivative of linoleic acid stimulates dehydroepiandrosterone production by human adrenal cells.

We previously reported that an oxidized derivative of linoleic acid stimulated steroidogenesis in rat adrenal cells. This derivative was also detected in human plasma, and was positively correlated with visceral adiposity and plasma DHEA-S. The present study sought to characterize the effects of this derivative, 12,13-epoxy-9-keto-(10- trans)-octadecenoic acid (EKODE), on steroid production by normal human adrenocortical cells obtained during clinically-indicated adrenalectomy. Cell suspensions were incubated in the presence of varying concentrations of EKODE and ACTH. EKODE (16 microM) significantly increased DHEA production by 28% under basal conditions and by 25% in the presence of a low concentration of ACTH (0.2 ng/ml). The effect on DHEA was absent at a higher ACTH concentration (2.0 ng/ml). EKODE decreased cortisol production by 16% (low ACTH) and 25% (high ACTH), but was without effect on cortisol under basal conditions. The results suggest that EKODE affects adrenal DHEA production in the human, possibly by modulating steroidogenic enzyme activity. We postulate that excess visceral fat delivers fatty acids to the liver, where oxidized derivatives are formed that modulate adrenal steroidogenesis. This may be an important phenomenon in the genesis of changes in adrenal function associated with syndromes of obesity, especially those that include androgen excess.

Adrenal Glands↗

PubMed2006

Adrenal lipid profiles of chemically sympathectomized normoxic and hypoxic neonatal rats.

Neonatal hypoxia is a common condition that elicits a coordinated endocrine response. In the neonatal rat, hypoxia induces an ACTH-independent increase in corticosterone which can be partially blocked by chemical sympathectomy. The present study sought to characterize the effects of sympathectomy on the adrenal lipid profile, since previous work suggested that augmented plasma corticosterone during hypoxia may be due to changes in adrenal lipid metabolism. Newborn rats were exposed to normoxia or hypoxia from birth to seven days of age, and guanethidine was used to produce the sympathectomy. Plasma epinephrine and norepinephrine were not significantly affected by hypoxia, while guanethidine decreased plasma norepinephrine in normoxic and hypoxic pups. Hypoxia alone increased the concentration of cholesterol esters in the adrenal gland; this increase was due to increases in cholesterol ester-associated oleic (18:1n9), docosahexaenoic (22:6n3), arachidonic (20:4n6), and adrenic (22:4n6) acids. Hypoxia also increased diglyceride-associated adrenic acid. Guanethidine treatment attenuated the hypoxia-induced increase in cholesterol ester-bound arachidonic and adrenic acids. Guanethidine also decreased saturated fatty acid concentrations and increased n3 fatty acid-enriched triglycerides. The results support the idea that the ACTH-independent corticosterone response to hypoxia in the neonatal rat is mediated by specific, sympathetically driven alterations in the adrenal lipid profile.

Adrenal Glands↗

PubMed2002

Oxidized products of linoleic acid stimulate adrenal steroidogenesis.

Adrenal steroidogenesis is under complex control, and clinical observations suggest that not all regulators have been identified. We postulated that fatty acid oxidation products found in the diet or formed in the body could affect steroidogenesis. Linoleic acid is a prominent constituent of animal fat and is readily oxidized. We found that several products of linoleic acid oxidation affect production of aldosterone and corticosterone by isolated cells from rat adrenals. We characterized one linoleic acid derivative by gas chromatography/mass spectrometry. It is 12,13-epoxy-9-oxo-10(trans)-octadecenoic acid ("EKODE"). At concentrations between 1 and 30 microM, EKODE stimulated production of aldosterone by zona glomerulosa cells, but at concentrations above 50 microM, it was inhibitory. In zona fasciculata cells, EKODE stimulated corticosterone production at concentrations of 5 microM or greater, and there was no evidence of inhibition at high concentrations. Stimulation of steroidogenesis was observed after 15 min of incubation and continued for at least 2 hrs. The potential relevance of our findings to the hypertension of obesity is discussed.

Aldosterone↗

PubMed2002

Oxygen-dependence of ACTH-stimulated aldosterone and corticosterone synthesis in the rat adrenal cortex: developmental aspects.

The control of ACTH-stimulated steroidogenesis under decreasing levels of O(2) is not fully understood. The purpose of this study was to examine the effects of decreased O(2) in vitro on rat adrenocortical steroid synthesis at different stages of development. Of interest was the evaluation of the effect of low O(2) on steroidogenesis during the stress hyporesponsive period of the neonate. Rats were killed at 7, 14, or 42 days of age, adrenals collected and capsules (zona glomerulosa, ZG) separated from subcapsules (zona fasciculata/reticularis, ZFR). Cells were dispersed and placed into glass vials each gassed with a different level of O(2) (21, 5, 2, 1, or 0% O(2)). The entire steroidogenic pathway was analyzed by measuring ACTH-stimulated cAMP, corticosterone and aldosterone production during a 2 h incubation. In addition, the early (P450 scc) and late (P450c11 beta and P450 aldo) pathway activities were examined in the presence of cyanoketone. The PO(2) for half-maximal activity (P(50)) for aldosterone synthesis in ZG cells from 7- and 42-day-old rats was approximately 28 mmHg and 7 mmHg respectively, indicating that cells from older rats were more resistant to inhibition by low O(2). The P(50) for cAMP production from the ZG was approximately 14 mmHg for both age groups. The P(50) for corticosterone synthesis was approximately 28 mmHg and <7 mmHg in ZFR cells from 7- and 42-day-old cells respectively. The only enzyme activities affected by low O(2) (<35 mmHg) were P450 aldo and P450 scc. Moderate decreases in O(2) (from approximately 150 mmHg) decreased aldosteronogenesis, possibly due to observed decreases in cAMP generation, but not due to decreases in steroidogenic enzyme activity (7-day-old). Severe decreases in O(2) presumably inhibited P450 aldo through a direct effect on enzyme activity (both ages). P450 scc activity (including cholesterol transport) also seems to be decreased by very low O(2) (7-day-old). These findings illustrate a novel developmental alteration in O(2)-regulated steroid production, and may have implications for neonatal health and disease.

Adrenal Cortex Hormones↗

PubMed2001

Diagnosis and differential diagnosis of Cushing's syndrome.

The clinical recognition of Cushing's syndrome and its biochemical confirmation is a challenging problem. The best diagnostic approach to patients with suspected Cushing's syndrome is still evolving. The traditional diagnostic approach of urine free cortisol and low-dose dexamethasone suppression testing may be inadequate when the degree of hypercortisolism is mild. Late-night salivary cortisol determinations may evolve as the simplest means of screening patients for suspected hypercortisolism. Repeated measurements of cortisol secretion (urine free cortisol or late-night salivary cortisol) over an extended period of time may be necessary to provide diagnostic certainty. The dexamethasone-CRH test is a reasonable approach in patients with equivocal data. The introduction of reliable, sensitive, and specific plasma ACTH measurements, the use of IPSS for ACTH with CRH stimulation, and the improved techniques of pituitary and adrenal imaging have made the differential diagnosis of Cushing's syndrome relatively straightforward (see Fig. 2). Clinicians who have never missed the diagnosis of Cushing's syndrome or have never been fooled by attempting to establish its cause should refer their patients with suspected hypercortisolism to someone who has.

Cushing Syndrome↗

PubMed2001

Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.

BACKGROUND: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels. OBJECTIVES: 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression. METHODS: Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level. RESULTS: One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results. CONCLUSIONS: Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.

Administration, Inhalation↗

PubMed2001

Effect of neonatal hypoxia on leptin, insulin, growth hormone and body composition in the rat.

The purpose of the present study was to evaluate the effect of exposure to hypoxia from birth to 7 days of age on leptin, insulin, growth hormone (GH), insulin-like growth factor-1 (IGF-1), glucose, corticosterone, body weight, and body composition in rats studied at 7 days of age and then after return to normoxia. Hypoxia for the first 7 days of life resulted in a significant decrease in plasma leptin, body weight, and an increase in corticosterone and insulin with no change in plasma glucose, GH or IGF-1. There was no significant effect of hypoxia on % lean body mass, but a small but significant increase in % body fat. Bone mineral density (BMD) was lower in 7-day-old hypoxic rats as compared to normoxic controls. All hormonal variables and BMD had normalized by 7 days after return to normoxia. However, body weight remained lower even 5 weeks after return to normoxia. We conclude that leptin is decreased during neonatal hypoxia despite no change in adiposity. Furthermore, insulin is increased probably to overcome the effects of increased counterregulatory hormones (such as corticosterone).

Animals↗

PubMed2001

Mandibular and palatal tori, bone mineral density, and salivary cortisol in community-dwelling elderly men and women.

BACKGROUND: This investigation evaluated the relationship between the presence of tori and bone mineral density (BMD) and salivary cortisol levels. METHODS: A total of 230 healthy, community-dwelling elderly men (n = 129) and women (n = 101) aged 60 and older participated in this study. Forty-three women were on hormone replacement therapy (HRT). This was a component of a 5-year longitudinal study measuring subjects' body composition, hormone levels, physical activity, and diet every 6 months. Subjects were examined for the presence of tori by visual inspection and digital palpation. BMD at six sites was measured by dual-energy X-ray absorptiometry. Salivary cortisol levels were measured by radioimmunoassay. RESULTS: Twenty-three percent of all subjects had mandibular tori, 13% had palatal tori, and 12% had both mandibular and palatal tori. Mandibular tori were more common in men, and palatal tori were more common in women. The presence of mandibular tori was significantly correlated with BMD of the lumbar spine, femoral neck, trochanter, and Ward's triangle for all subjects, and with the femoral neck and trochanter of women not on HRT. Men with palatal tori had lower levels of salivary cortisol in the evening. CONCLUSIONS: This study documented the high prevalence of mandibular and palatal tori in a group of 230 elderly, community-dwelling subjects. Women not on HRT and all subjects taken as a group with mandibular tori had higher BMD. The presence of tori at young adulthood may be a marker of higher BMD in the future and of a lower risk for developing osteoporosis.

Aged↗

PubMed2001

Comparison of adrenal vein sampling and computed tomography in the differentiation of primary aldosteronism.

Determination of the etiology of primary aldosteronism remains a diagnostic challenge. The most common types of primary aldosteronism are bilateral adrenal hyperplasia (BAH), aldosterone-producing adenomas (APA), and primary adrenal hyperplasia. Computed tomography (CT) and adrenal vein sampling (AVS) are the primary modalities used to differentiate these subtypes. The purpose of this study was to compare AVS and CT imaging of the adrenal glands in patients with hyperaldosteronism in whom CT imaging was normal or in whom focal unilateral or bilateral adrenal abnormalities were detected. The diagnosis of primary aldosteronism was made in 62 patients based on an elevated plasma aldosterone to PRA ratio and an elevated urinary aldosterone excretion rate. Thirty-eight patients had CT imaging and successful bilateral adrenal vein sampling and were included in the final analysis. AVS was considered the gold standard in determining the specific subtype of primary aldosteronism. There were 15 patients with APA, 21 patients with BAH, and 2 patients with primary adrenal hyperplasia. Plasma aldosterone was significantly higher in patients with APA (46.3 +/- 8.5 ng/dL; 1284 +/- 235 pmol/L) than in those with BAH (29.3 +/- 2.4 ng/dL; 813 +/- 11 pmol/L; P < 0.05). Plasma potassium was significantly lower in patients with APA (3.1 +/- 0.1 mmol/L) than in patients with BAH (3.5 +/- 0.1 mmol/L; P < 0.02). There was considerable overlap in the other biochemical indices (e.g. PRA and urinary aldosterone) in patients with the different subtypes. In patients with APA proven by AVS, eight had concordant findings with CT imaging, four had discordant findings, and three had normal CT imaging. In patients with BAH proven by AVS, four had concordant findings with CT imaging, eight had discordant findings, and nine had normal CT imaging. Compared with AVS, CT imaging was either inaccurate or provided no additional information in 68% of the patients with primary aldosteronism. We conclude that adrenal CT imaging is not a reliable method to differentiate primary aldosteronism. Adrenal vein sampling is essential to establish the correct diagnosis of primary aldosteronism.

Adenoma↗

PubMed2001

Growth hormone therapy during neonatal hypoxia in rats: body composition, bone mineral density, and insulin-like growth factor-1 expression.

Hypoxia from birth results in a decrease in body weight gain, body size, and bone mineral density (BMD). The purpose of the present study was to determine whether short-term administration of growth hormone (GH) (rat GH; 100 microg/d) could attenuate some of these effects of neonatal hypoxia. Rat pups (with their lactating dams) were exposed to hypoxia (vs normoxic control) from birth. Hypoxia was continued until 14 d of age, with rat GH (vs vehicle control) administered daily. Hypoxia significantly inhibited body weight gain; GH therapy did not reverse this effect. GH therapy did reverse the inhibitory effect of hypoxia on tail length but not on body length. Hypoxia decreased BMD analyzed by dual X-ray absorptiometry (DXA); this effect was not reversed by GH therapy. Both GH therapy and hypoxia decreased the percentage of body fat analyzed by DXA, the effects of which were additive when combined. There were minimal effects of hypoxia and GH therapy on plasma insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, and hepatic IGF-1 mRNA expression. We conclude that some of the effects of hypoxia on body habitus are reversed by GH therapy, but that short-term GH therapy did not prevent a loss of BMD. GH therapy for more than 14 days may be necessary to appreciate fully its potential in the treatment of the sequelae of neonatal hypoxia.

Animals↗

PubMed2000

Neonatal hypoxic hyperlipidemia in the rat: effects on aldosterone and corticosterone synthesis in vitro.

Neonatal hypoxia increases aldosterone production and plasma lipids. Because fatty acids can inhibit aldosterone synthesis, we hypothesized that increases in plasma lipids restrain aldosteronogenesis in the hypoxic neonate. We exposed rats to 7 days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of age (weaned at day 21). Plasma was analyzed for lipid content, and steroidogenesis was studied in dispersed whole adrenal glands untreated and treated to wash away lipids. Hypoxia increased plasma cholesterol, triglycerides, and nonesterified fatty acids in the suckling neonatal rat only. Washing away lipids increased aldosterone production in cells from 7-day-old rats exposed to hypoxia, but not in cells from normoxic 7-day-old rats or from normoxic or hypoxic 35-day-old rats. Addition of oleic or linolenic acid to washed cells inhibited both aldosterone and corticosterone production, although cells from hypoxic 7-day-old rats were less sensitive. We conclude that hypoxia induces hyperlipidemia in the suckling neonate and that elevated nonesterified fatty acids inhibit aldosteronogenesis.

Adrenal Glands↗

PubMed2000

Effect of neonatal hypoxia on the development of hepatic lipase in the rat.

Increases in plasma lipids occur during hypoxia in suckling but not in weaned rats and may result from altered hepatic enzyme activity. We exposed rats to 7 days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of age (weaned at day 21). Hypoxia led to an increase in hepatic lipid content in the suckling rat only. Hepatic lipase was decreased to approximately 45% of control in 7-day-old rats exposed to hypoxia but not in hypoxic 35-day-old rats. Hypoxic suckling rats also had a 50% reduction in lactate dehydrogenase activity, whereas transaminase activity and CYP1A and CYP3A protein content were not different between hypoxic and normoxic groups. Additional rats were studied 7 and 14 days after recovery from hypoxic exposure from birth to 7 days of age; hepatic lipase activity had recovered to 85% by 7 days and to 100% by 14 days in the rats previously exposed to hypoxia. Administration of dexamethasone to neonatal rats to simulate the hyperglucocorticoid state found in hypoxic 7-day-old rats led to a moderate decrease ( approximately 75% of control) in hepatic lipases. Developmentally, in the normoxic state, hepatic lipases increased rapidly after birth and reached levels more than twofold that of the newborn by 7 days of age. Hypoxia delays the maturation of hepatic lipases. We suggest that the decrease in hepatic lipase activity contributes to hyperlipemia in the hypoxic newborn rats.

Aging↗

PubMed2000

The effect of fetal hypoxia on adrenocortical function in the 7-day-old rat.

Fetal hypoxia in late gestation is a common cause of postnatal morbidity. The purpose of the present study was to evaluate adrenal function in vivo and in vitro in 7-d-old rat pups previously exposed to normoxia or hypoxia (12% O2) during the last 2-3 d of gestation. Seven-day-old rats exposed to fetal hypoxia had a small, but significant decrease in plasma aldosterone despite no decreases in plasma ACTH or renin activity. There was a small (approx 20%) but significant decrease in the aldosterone and corticosterone response to cAMP in vitro in dispersed cells from 7-d-old pups exposed to fetal hypoxia. The aldosterone, corticosterone, and cAMP response to ACTH, however, was not altered by prior fetal hypoxia. There was also no effect of fetal hypoxia on steroidogenic enzyme expression or zonal dimension in 7-d-old rats. We conclude that fetal hypoxia in late gestation results in a subtle decrease in cAMP-stimulated steroidogenesis. Fetal hypoxia appears to have minimal effects on subsequent adrenal function in the neonatal rat.

Adrenal Cortex↗

PubMed2000

Randomized trial of oral hydrocortisone and its effect on emergency physicians during night duty.

STUDY OBJECTIVE: To analyze the effects of hydrocortisone (40 mg. p.o.) administered to emergency physicians on their first night shift following a series of day shifts. DESIGN: Prospective, double-blinded internal crossover study on objective and subjective parameters. Each participant was studied for a minimum of 10 nights. TYPE OF PARTICIPANTS: Four healthy male emergency physicians in their mid to late thirties. INTERVENTIONS: After baseline endocrine assessment, the subjects ingested a capsule containing either 40 mg of hydrocortisone or placebo (lactose) at the start of a first nightshift (starting at 10 pm or 11 pm) after day duty. Subjects self-administered psychological testing one hour after taking an oral capsule by listening to a self-guided audio tape (between 11 and 12 p.m), and again between 4 and 5 am. Blood samples were obtained during the first 4 nights of each subject at 11 pm, 2, 5 and 8 am. MEASUREMENTS AND MAIN RESULTS: Four emergency physicians entered 42 nights of data. No differences in testing were detected. Plasma cortisol levels were measured and demonstrated cortisol levels consistent with oral replacement therapy. Physicians could subjectively differentiate the difference between hydrocortisone treatment and placebo: of 21 hydrocortisone nights, 17 were identified as "a good night" in reference to fatigue. Of 21 nights without hydrocortisone, 15 were identified as "bad" nights, (p < .001). CONCLUSION: Hydrocortisone, administered before a nightshift to day-accommodated workers, recreated the rise of plasma cortisol seen on awakening and was shown to be an effective means of decreasing subjective fatigue of a first nightshift.

Administration, Oral↗

PubMed1999

Newer diagnostic techniques and problems in Cushing's disease.

The best diagnostic approach to patients with suspected Cushing's disease continues to evolve. The introduction of transsphenoidal pituitary surgery as the treatment of choice for Cushing's disease as well as the absence of any pituitary imaging abnormalities in many patients with Cushing's disease has made accurate diagnosis and differential diagnosis essential. In the authors' opinion, two or three late night (11 PM) salivary cortisol determinations and the measurement of 24-hour UFC are the best and simplest means to evaluate patients with suspected hypercortisolism. L-DST can no longer be recommended to exclude the diagnosis of Cushing's disease, particularly if the hypercortisolism is mild. The combination of L-DST and CRH stimulation is a new and apparently sensitive means to establish the presence or absence of pathologic hypercortisolism in equivocal cases. In the absence of an overt pituitary tumor on MR imaging, inferior petrosal sinus sampling with CRH stimulation should be performed to secure the diagnosis of Cushing's disease as well as identify the probable location of the corticotroph adenoma.

Adrenocorticotropic Hormone↗

PubMed1999

Elevated salivary cortisol in the evening in healthy elderly men and women: correlation with bone mineral density.

BACKGROUND: Aging is associated with a loss of bone mineral density (BMD) in men and women. Loss of BMD can also be caused by hypercortisolemia in men or women at any age. This study measured salivary cortisol at 2300 h and 0700 h as indices of cortisol secretory activity in 228 elderly, community-dwelling subjects. Salivary cortisol results were correlated with BMD. We hypothesized that salivary cortisol is elevated at 2300 h in elderly people, and that salivary cortisol will correlate negatively with BMD. METHODS: Saliva was sampled at 2300 h (nadir in circadian rhythm) and 0700 h (peak in circadian rhythm) in 130 men (70.7 +/- 0.4 years old) and 98 women (70.0 +/- 0.4 years old); approximately half of the women were receiving hormone replacement therapy (HRT). BMD was measured by dual energy x-ray absorptiometry. RESULTS: Salivary cortisol at 2300 h was significantly elevated in men (2.3 +/- 0.1 nmol/L) and women (2.1 +/- 0.1 nmol/L) as compared to 73 younger controls (1.2 +/- 0.1 nmol/L; 37 +/- 1 year old). Salivary cortisol at 0700 h was not different between older subjects and younger controls. There was a significant negative correlation of lumbar (L2-4) BMD and 2300 h salivary cortisol in older women (r = -0.20, p = .05; n = 98); this correlation was significant only in women not on HRT. There was a highly significant negative correlation of lumbar (L2-4) BMD and 0700 h salivary cortisol in older men (r = -0.31, p = .0003). CONCLUSIONS: Salivary cortisol is a simple, nonstressful method for assessing activity of the hypothalamic-pituitary-adrenal (HPA) axis in the elderly population. A major finding was an elevation in the late night nadir in cortisol secretion. We also suggest that elevated cortisol secretion in elderly people may contribute to the age-related loss in bone mineral density and that this effect is prevented by HRT.

Aged↗

PubMed1999

The effect of hypoxia from birth on the regulation of aldosterone in the 7-day-old rat: plasma hormones, steroidogenesis in vitro, and steroidogenic enzyme messenger ribonucleic acid.

Adaptation to hypoxia in the neonate requires an appropriate adrenocortical response. The purpose of this study was to examine the adaptation of the aldosterone pathway in rat pups exposed to hypoxia in vivo from birth to 7 days of age. Neonatal rats (with their lactating dams) were exposed to normoxia (21% O2) or hypoxia (12% O2) continuously for 7 days from birth. Trunk blood was collected, and entire adrenal glands were processed from 7-day-old rats to study the activity of the steroidogenic pathway in dispersed cells and isolated mitochondria, for measurement of expression of the steroidogenic enzyme messenger RNAs (mRNAs) by RT-competitive PCR and in situ hybridization histochemistry, for measurement of zona glomerulosa width by immunohistofluorescent staining for P450c11AS protein, and for measurement of mitochondrial number and distribution by transmission electron microscopy. Exposure to hypoxia for 7 days from birth resulted in a marked increase in plasma ACTH, corticosterone, and aldosterone with no change in PRA. Aldosteronogenesis and P450c11AS activity were both augmented in dispersed cells; this effect was lost in isolated mitochondria (from entire adrenal glands) using a permeable substrate for P450c11AS. There was no significant effect of hypoxia on expression of the steroidogenic enzyme mRNAs measured by RT-competitive PCR or in situ hybridization histochemistry. Finally, hypoxia had no effect on mitochondrial number or stereology as assessed by transmission electron microscopy or on zona glomerulosa width as assessed by staining for P450c11AS protein. We conclude that, as opposed to that in adults, hypoxia in the neonate results in an augmentation of aldosteronogenesis. This effect is not accounted for by a change in steroidogenic enzyme mRNA expression, zona glomerulosa width (i.e. hyperplasia), or mitochondrial number or distribution. This functional augmentation of aldosteronogenesis may be due to a change in mitochondrial permeability to steroid substrates and/or the effect of cytosolic factors that control mitochondrial steroidogenesis.

Adrenal Cortex↗

PubMed1999

The effect of hypoxia on plasma leptin and insulin in newborn and juvenile rats.

Hypoxia leads to a decrease in food intake and attenuated weight gain in rats. The purpose of this study was to measure plasma leptin and insulin in young rats exposed to hypoxia for 7 d as compared to a normoxic control group of the same age. One group was exposed from birth to 7 d of age; the other was exposed from 28 to 35 d of age (weaned at 21 d of age). As expected, body weight was significantly lower in rats of either age exposed to hypoxia for 7 d. Plasma leptin was significantly lower in hypoxic (2.0+/-0.2 ng/mL; n = 41) compared with normoxic (2.6+/-0.3 ng/mL; n = 30) 7-d-old rats. Plasma leptin was also significantly lower in hypoxic (1.1+/-0.1 ng/mL; n = 20) as compared to normoxic (1.5+/-0.1 ng/mL; n = 20) 35-d-old rats. Seven-day-old rats exposed to hypoxia demonstrated significant increases in plasma glucose and insulin whereas 35-d-old rats exhibited a decrease in both variables. We conclude that exposure to hypoxia for 7 d leads to a decrease in body weight and plasma leptin in infant and juvenile rats. The decrease in leptin may be an attempt to reverse hypoxia-induced anorexia.

Aging↗