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W D Odell

Publications and source records attributed to W D Odell.

At least 55 records · Page 3Linked to original sources
PubMed1989

Pulsatile secretion of chorionic gonadotropin during the normal menstrual cycle.

Several groups of investigators have previously reported that small amounts of hCG are present in blood and urine of nonpregnant eugonadal women and men. We have developed highly sensitive and specific, two-monoclonal antibody, sandwich-type assays which can quantify both hCG and LH in sera from postmenopausal women, women at all phases of the menstrual cycle, and men. Using these assays we have also reported that hCG is secreted in a pulsatile fashion in postmenopausal women, is stimulated by GnRH in both men and postmenopausal women, and is suppressed by a GnRH agonist in castrate men. Employing these same sandwich assays, we report herein that hCG is secreted in a pulsatile manner during the follicular and luteal phases of the normal menstrual cycle. During the follicular phase 0.68 +/- 09 (+/- SEM) pulses of hCG occurred each hour, while 0.62 +/- 0.08 pulses of LH occurred. Pulse durations during the follicular phase for hCG and LH, respectively, were 38.3 +/- 4.4 and 62.5 +/- 11.1 min (P less than or equal to 0.05). During the luteal phase there were 0.42 +/- 0.16 pulses/h of hCG and 0.38 +/- 0.08 pulses of LH (P greater than 0.05). Pulse durations were 22.3 +/- 7.5 and 126.4 +/- 19.0 min for hCG and LH, respectively (P less than 0.01). The t1/2 of hCG disappearance was 37.2 +/- 3.8 min during the follicular phase and 22.9 +/- 4.6 min during the luteal phase. The t1/2 values of LH were 82.9 +/- 5.7 and 67.5 +/- 5.12 min during follicular and luteal phases, respectively. The t1/2 of LH was greater than the t1/2 of hCG (P less than 0.01). We conclude that small amounts of hCG are secreted in a pulsatile manner during follicular and luteal phases of the human menstrual cycle.

Adult↗
PubMed1989

Immunoradiometric assay of corticotropin with use of avidin-biotin separation.

We have developed a "sandwich"-type immunoradiometric assay for corticotropin (ACTH), with a detection limit of 2 ng/L. Two antibodies are used: a mouse monoclonal antibody directed against ACTH[1-17] and labeled with 125I; and a purified polyclonal goat antibody directed against ACTH[34-39] and conjugated to biotin. We could separate 125I-labeled antibody bound to ACTH from 125I-labeled antibody not bound to ACTH by using an avidin-biotin bridge, with avidin bound to a polystyrene ball. This assay reacts with ACTH[1-39] but shows no reaction with ACTH fragments [1-24], [1-17], or [34-39], or with melanotropin, endorphins, or lipotropin. This assay is sensitive enough to detect ACTH in plasma of all normal adults. Concentrations measured in 94 adults between 0800 and 1000 hours were normally distributed on a log scale, with a mean of 19.5 ng/L and a 95% range of 7.1 to 53.8 ng/L. Dexamethasone given at 2300 hours to 14 adults suppressed ACTH to less than 4 ng/L in 13 of the subjects and to 8 ng/L in the 14th. Metyrapone given to 13 adults at 2300 hours increased ACTH to 245.3 ng/L (95% range, 90.1 to 667.7 ng/L). This assay accurately classified patients with disorders of the adrenal system.

Adrenocorticotropic Hormone↗
PubMed1989

Paraendocrine syndromes of cancer.

Understanding of the humoral manifestations of cancer has steadily increased over recent years. The endocrine syndromes, where they are understood, appear to be caused by increased production by the cancer of protein hormones, protein hormone precursors, or protein hormone-like substances. These proteins are commonly produced also by nonneoplastic, nonendocrine cells, and presumably represent paracrine or autocrine substances. Many of the neurologic syndromes, and possibly a wide range of other paraneoplastic syndromes, appear to be caused by tumor immunogen stimulation of antibodies that cross-react not only with the specific tumor antigen but also with antigens from host tissues. Antibody-mediated cell injury leads to the specific symptoms, determined by the tissue injured. Some of the hematologic paraneoplastic syndromes (e.g., aplastic anemia, red cell aplasia) may also be produced by immune mechanisms. Finally, at least one syndrome, multifocal leukoencephalopathy, is caused by a viral infection. Presumably the host with cancer is more susceptible to such infections. The pathogenesis of many syndromes caused by cancers remains unclear. The amino acid structure of the hormones produced by cancers has not been determined for any of the syndromes. The function of these protein hormones produced by normal, nonendocrine tissues is unknown.

Endocrine System Diseases↗
PubMed1988

Identification of LH/hCG receptors in rabbit uterus.

Luteinizing hormone (LH) is believed to act via specific receptors to control gonadal steroidogenesis and reproductive processes. Recently A. J. Ziecik, P. D. Stanchev, and J. E. Tilton (Endocrinology 119:1159, 1986) reported surprisingly that LH/hCG receptors were present in porcine uterus, a tissue not known to be a target for LH action. We report herein the identification of high-affinity LH receptors in the rabbit uterus. Uteri from adult New Zealand white rabbits were homogenized in Tris-HCl, 0.25 M sucrose. After filtration and sequential centrifugation, a partially purified pellet containing receptors was obtained. This preparation was incubated with a trace (1300 cpm) (50 pg) 125I-labeled chorionic gonadotropin and with various unlabeled protein hormones. Receptor bound was separated from free hormone by centrifugation at 1000 g. Affinity was estimated by Woolf plot analysis. Specific binding sites for LH/hCG were identified. The following Kd's were calculated: human LH, 1.6 X 10(-11); hCG, 0.5 X 10(-11); human TSH, 1.3 X 10(-9); and human FSH, 7.85 X 10(-9). The reaction of human FSH and TSH with the receptor is best explained by LH contamination of these hormones. A similar preparation of rat liver showed that no binding sites were present. Rabbit ovarian LH receptors had a Kd slightly higher at 4.1 X 10(-11) than that of the uterine LH receptors. Rabbit ovarian receptors were present at 2.27 X 10(-13) M/mg protein compared to uterine receptors at 4.65 X 10(-15) M/mg protein. We conclude specific- and high-affinity binding sites (receptors) for LH are present in the rabbit uterus. The function of these receptors remains unknown.

Animals↗
PubMed1987

Pulsatile secretion of human chorionic gonadotropin in normal adults.

We used very sensitive and specific monoclonal-antibody sandwich assays for human chorionic gonadotropin (hCG) and human luteinizing hormone (hLH) to measure both hormones in serum samples from normal men and women. When single serum samples from 92 men were studied, 73 percent had detectable hCG. In normal men, the amount of detectable hCG averaged 8.9 pg per milliliter, with a range of less than 3.0 to 160 pg per milliliter (biologic potency = 13,450 IU per milligram). In postmenopausal women the hCG level averaged 111 pg per milliliter and ranged from 32 to 510. In women of reproductive age the hCG level varied with the menstrual cycle. Gonadotropin-releasing hormone administered to 10 normal men increased both hCG and hLH. When daily serum samples were studied throughout a normal menstrual cycle, hCG concentrations paralleled those of hLH; follicular-phase concentrations were higher than those of the luteal phase, and there was a midcycle ovulatory peak of hCG coincident with the hLH peak. When hCG was measured every 10 minutes for six hours in eight postmenopausal women, distinct pulses were detected in parallel with those of hLH: hLH pulsed at a mean (+/- SEM) frequency of 0.56 +/- 0.08 pulses per hour; hCG pulsed at 0.54 +/- 0.07 pulses per hour. The mean pulse durations were 89 +/- 22 and 56 +/- 20 minutes for hLH and hCG, respectively. We conclude that hCG is produced in a pulsatile fashion, probably by the pituitary, in all normal adults.

Adult↗
PubMed1987

Ultrasensitive immunoradiometric assay for chorionic gonadotropin which does not cross-react with luteinizing hormone nor free beta chain of hCG and which detects hCG in blood of non-pregnant humans.

We have developed a sensitive, non-competitive, two-monoclonal antibody, sandwich-type or immunoradiometric assay for human chorionic gonadotropin (hCG) which shows no cross-reaction with the free beta chain of hCG nor with human luteinizing hormone (LH). In the assay procedure, two, highly selected monoclonal antibodies reacted in solution with hCG to be quantified. One antibody was covalently conjugated to biotin. This antibody was specific for the beta subunit of hCG, and showed no reaction with LH nor the alpha subunit. The second antibody was labelled with 125I and was specific for intact hCG and LH, showing no cross-reaction with beta hCG nor the alpha subunit. The separation system was a polystyrene ball conjugated with biotin. This ball bound via an avidin bridge the monoclonal 'sandwich' containing hCG. Counts per minute bound to the ball were directly proportional to the amount of hCG present. The assay was specific for whole hCG and showed no reaction with beta hCG, beta LH, intact LH nor the free alpha subunit. Sensitivity was adequate to detect 'hCG-like' material in all post menopausal women and, when single samples were obtained, in over 2/3 of normal men. When multiple samples were obtained, 'hCG-like' material was detectable in all eugonadal adults studied.

Antibodies, Monoclonal↗
PubMed1987

Prolactin alters luteinizing hormone pulsation characteristics in the intact and castrate male rabbit.

The effect of prolactin (PRL) on luteinizing hormone (LH) pulsation characteristics in intact and castrate male rabbits was investigated. Eight groups of animals were studied. Two groups castrate and two groups of adult male rabbits served as controls to establish baseline pulsation characteristics. Preliminary studies showed that a sampling interval of 3-4 min was optimal. One group of castrate and one group of intact rabbits were sampled at this frequency for 60 min; two additional groups were sampled for 240 min. With these data determined, four groups were used in paired studies: two castrate and two intact groups received either a bolus injection intravenously of saline or PRL (20 micrograms), followed by a constant infusion of saline or PRL (50 micrograms/min) for 3.5 h. Blood was sampled every 3 min for the last 1.5 h of infusion. Serum LH was measured on each sample; rabbit PRL was measured on pooled samples. In selected samples bovine PRL was also measured. The LH pulsation characteristics of the 3 groups of castrate and intact controls (unperfused and saline-perfused) were not statistically different and the data were pooled. The PRL-treated animals were compared to the controls. Castration increased LH mean concentration, pulse amplitude and duration. PRL infusion decreased mean LH concentration and pulse amplitude in both intact and castrate animals. Pulse duration was decreased significantly in castrate, but not in intact, animals by PRL infusion. We conclude that, in the adult male rabbit, PRL modulates LH pulsation. This action of PRL must occur either directly at the pituitary or more probably through an influence on gonadotropin-releasing hormone pulsation at the hypothalamus.

Animals↗
PubMed1987

Two-monoclonal-antibody "sandwich"-type assay of human lutropin, with no cross reaction with choriogonadotropin.

We have developed a sensitive, specific, noncompetitive sandwich-type assay for human lutropin (hLH). Two monoclonal antibodies are used, and there is no cross reaction with human choriogonadotropin (hCG) or human follitropin (hFSH), and little or none with human thyrotropin (hTSH). There also is no reaction with the free beta chains of hLH and hCG. The detection limit is less than 0.5 int. units of hLH per liter of serum, and the dose-response curve is linear between 0 and 10 int. units/L. The intra-assay CV averaged 5.4% at low doses of hLH; the interassay CV averaged 12.5%.

Antibodies, Monoclonal↗
PubMed1986

Primary adrenocortical nodular dysplasia, a distinct subtype of Cushing's syndrome. Case report and review of the literature.

Non-iatrogenic Cushing's syndrome has been associated primarily with three entities: pituitary-dependent processes due to pituitary adenomas or microadenomas causing adrenal hyperplasia; pituitary-independent primary adrenal causes, predominantly unilateral adenomas, rarely multiple adenomas or adrenal carcinoma; ectopic sources of adrenocorticotropic hormone (ACTH) production. Although non-neoplastic bilateral adrenal disease generally has been ascribed to extra-adrenal stimulation, a rare cause of Cushing's syndrome that involves bilateral adrenal nodule formation independent of pituitary stimulation has been identified. Nodular adrenal diseases represent a confusion of terms in the literature, but one subgroup of Cushing's syndrome has most frequently--and, perhaps, most appropriately--been designated primary adrenocortical nodular dysplasia. A case of this unusual entity is presented, and previous case reports pertaining to this confusing area of adrenal hyperfunction are reviewed. The characteristic manifestations that separate this diagnosis from other types of nodular adrenal disease are also discussed. Recognition of this diagnosis, although rare, is important, as bilateral adrenalectomy in the treatment of choice.

Adolescent↗
PubMed1986

The clinical track.

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Faculty, Medical↗
PubMed1986

Pituitary gland: one site of ultrashort-feedback regulation for control of thyrotropin.

Studies from our laboratory have previously demonstrated sensitive and specific autoregulatory control systems for thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the rabbit. Because our studies of LH autoregulation showed the feedback regulation acted directly at a pituitary level, the current studies were designed to investigate whether the TSH control system also acted at the pituitary level. Two species-specific TSH assays were employed; a rabbit TSH radioimmunoassay which showed little or no reaction to human TSH, and a human TSH radioimmunoassay which showed little or no reaction to rabbit TSH. Both in vivo and in vitro studies were performed. TRH (thyrotropin-releasing hormone) in doses of 2, 10, and 50 micrograms was injected as an intravenous bolus into thyroidectomized hypothyroid rabbits during continuous perfusion with highly purified human TSH (hTSH) or with saline. In these in vivo studies, TRH-stimulated rabbit TSH (rTSH) secretion was suppressed by hTSH perfusion compared with control saline perfusion. The effect of hTSH was studied in vitro by employing short-term cultured rabbit pituitary cells. When hTSH was added to the incubation medium, TRH-stimulated rTSH secretion was inhibited. From these studies, we conclude that one site of the autoregulatory control for TSH in the rabbit is at the pituitary level. These studies do not exclude a possible additional short-loop feedback control at an hypothalamic level, but such a site of action is not required to explain the autoregulatory phenomenon.

Animals↗
PubMed1986

Two-monoclonal-antibody sandwich-type assay for thyrotropin, with use of an avidin-biotin separation technique.

We have developed a sensitive, specific, noncompetitive, sandwich-type radioimmunoassay for human thyrotropin (hTSH), which can be performed in 30 min. The assay involves two monoclonal antibodies, selected for high affinity and specificity and also for reaction against antigenic sites on hTSH that are distal from each other. One of these antibodies is labeled with 125I; the other is conjugated covalently to biotin. Polystyrene beads were also conjugated covalently to biotin. After conjugation, the beads were incubated with avidin. These beads represent a rapid, simple method for separating hTSH-bound antibody from free antibody. The biotin-antibody-hTSH-125I-labeled antibody complexes bind to the beads and hTSH concentration is directly related to counts per minute. This assay can detect hTSH at a concentration of 0.06 milli-unit/L in serum.

Adult↗
PubMed1986

Effect of short- and long-term dexamethasone on 3 alpha-androstanediol glucuronide in hirsute women.

The role of glucocorticoid therapy in regulating plasma 3 alpha-androstanediol glucuronide (3 alpha-diol G) content, a marker of androgen action, in hirsute women was unclear. A pulse injection of adrenocorticotropic hormone (0.5 U) following 1 mg of dexamethasone (DEX) at midnight significantly increased the plasma level of cortisol (P less than 0.01), 17-hydroxyprogesterone (17-OHP, P less than 0.01) in 17 hirsute women, but it had an insignificant effect on delta 4-androstenedione (delta 4A), testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 3 alpha-diol G. Human chorionic gonadotropin administered for 3 days produced a significant (P less than 0.01) increase only in 17-OHP. DEX administered as a single dose in the late evening failed to affect the plasma levels of these four androgens when measured at 8:00 A.M. In contrast, when the glucocorticoid was given each evening for over 2 months, plasma delta 4A, DHEA-S, and 3 alpha-diol G were suppressed (P less than 0.001) substantially, as compared with baseline values in 12 hirsute women, 7 with polycystic ovary disease and 5 with idiopathic hirsutism. These observations indicate that chronic glucocorticoid therapy suppresses androgen action in hirsute women.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Unusual cause of short stature.

A 24-year-old man evaluated for paresthesias and short stature was found to be hypocalcemic on initial presentation. Further evaluation showed that he had a low-normal parathormone level by amino-terminal assay, medullary stenosis of the long bones, and multiple ophthalmologic abnormalities. The remainder of his pituitary function, including growth hormone response to insulin-induced hypoglycemia, was normal. As no family history of similar findings was evident, a sporadic case of Kenny's or Kenny-Caffey syndrome was diagnosed. He became normocalcemic in response to vitamin D and calcium carbonate therapy. The results of testing in this patient and the findings in other patients previously described with the Kenny-Caffey syndrome are reviewed.

Adult↗
PubMed1984

Effects of short-term hyperprolactinemia on the endocrine reproductive system in male rabbits.

We have systematically studied the effects of short-term hyperprolactinemia on reproductive function in male rabbits. Purified ovine prolactin (PRL) was administered intravenously, as bolus injections or by constant infusion, to unanesthetized animals bearing two chronically implanted Silastic catheters; blood samples were obtained via the second catheter. Short-term hyperprolactinemia did not modify serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations in either castrated or intact rabbits. However, in spite of no changes in LH and FSH, short-term PRL administration lowered the serum testosterone (T) in intact animals. Furthermore, while PRL had no effect on the LH and FSH response to gonadotropin-releasing hormone, it did inhibit the testicular secretion of T in response to the increased endogenous LH. PRL also inhibited human chorionic gonadotropin-stimulated T secretion by the testes. All of these studies indicate that PRL interferes with the testicular response to LH. The fact that LH and FSH did not rise in response to the lowered T in intact animals suggested that PRL also altered the steroid feedback control of LH and FSH secretion. To assess this, PRL or saline was repeatedly injected after castration. PRL prevented the postcastration rise in LH and FSH. These studies indicate that PRL acts at at least two sites in the reproductive system in rabbits: (1) directly at a gonadal level by interfering with gonadotropin action and (2) at a hypothalamic-pituitary central level by preventing the expected rise in gonadotropins in response to low gonadal steroids.

Animals↗
PubMed1984

Autoregulatory control of thyrotropin in rabbits.

Studies were designed to determine whether an autoregulation system exists for TSH in the rabbit. For this purpose, a species-specific RIA for rabbit TSH that does not cross-react with human (h) TSH was developed. Hypothyroid animals were studied at varying time periods up to 3 months after either surgical thyroidectomy or propylthiouracil (PTU) treatment. Highly purified hTSH was injected iv at doses of 0 (saline control), 0.1, 0.3, 1,3, and 10 micrograms into unanesthetized rabbits bearing chronically implanted Silastic catheters. Blood samples were obtained at -30, 0, 10, 20, 30, 60, 120, 180, 240, and 300 min and 24 h. Doses between 0.3 and 10 micrograms hTSH produced a prompt fall (10 min) in rabbit TSH in hypothyroid rabbits studied 8-21 days after thyroidectomy. The minimum dose of hTSH that significantly suppressed rabbit TSH was 0.3 micrograms. This dose produced a peak value of hTSH in rabbit serum of 1.3 +/- 0.1 (+/- SEM) ng/ml 10 min after injection, which translates into a bioassay potency of 2.0 microU/ml (close to the physiological level in humans). A dose-response relationship existed between the hTSH dose injected and the duration and magnitude of suppression of rabbit TSH. This response to TSH was specific; 10 micrograms hTSH produced no change in endogenous rabbit serum LH and, conversely, 10 IU hLH produced no change in rabbit serum TSH. In contrast to these striking effects in acute hypothyroid animals, hTSH produced no detectable suppression of rabbit TSH in animals that were hypothyroid for 2-3 months. The sensitivity of the autoregulatory system to the suppressive effects of exogenous hTSH decreased with increasing duration of hypothyroidism; a time-response relationship existed. We conclude that: 1) a sensitive and specific autoregulatory control system for TSH exists in the rabbit; and 2) as the duration of hypothyroidism increases, the sensitivity of the autoregulatory system to the suppressive effects of endogenous TSH changes.

Animals↗
PubMed1984

In vitro studies of prolactin inhibition of luteinizing hormone action on Leydig cells of rats and mice.

Previous in vivo studies have shown that in male rabbits prolactin inhibits the testosterone production stimulated by luteinizing hormone (LH) or human chorionic gonadotropin (hCG). This inhibition has now been studied in vitro using both mouse and rat testicular interstitial cells. First, the dose response of human LH (hLH) stimulation of testosterone was studied in detail using testicular interstitial cells from both species. Next, a small but stimulatory dose of hLH was selected and extensive prolactin doses were studied in vitro. NIH B-6 (bovine) prolactin in varying doses was added to the interstitial cells 30 min prior to the addition of a constant dose of hLH. Under these circumstances prolactin inhibited LH action over a wide range of doses. In both species a biphasic dose-response curve existed: large doses of 100 to 1000 ng/ml produced less inhibition or augmented LH action, compared to smaller doses. Next, entire hLH dose-response curves were produced in the presence of three doses of prolactin (0.33, 33, and 1000 ng/ml) as well as in the absence of prolactin. The addition of prolactin shifted the hLH dose-response curve to the right and depressed the maximal response in comparison to the curve without prolactin. Finally, inhibitory doses of prolactin resulted in no detectable change in LH receptor number as estimated from Scatchard plots. It is concluded that prolactin inhibits LH action on interstitial cells as determined by rate of testosterone production except at very large doses of prolactin where LH action is less inhibited or augmented. The inhibitory action of prolactin in this in vitro interstitial cell assay was not accompanied by a decrease in LH receptor number. Thus, a postreceptor action is likely to be involved.

Animals↗