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Biomedical subjects

V Padmanabhan

Publications and source records attributed to V Padmanabhan.

At least 73 records · Page 4Linked to original sources
PubMed1993

Accelerometer type cardiac transducer for detection of low-level heart sounds.

New applications in phonocardiography require transducers with high sensitivity, low noise, and extended frequency range. This paper compares several different cardiac transducers and describes the development of a low-mass, accelerometer type cardiac transducer which fulfills these objectives. The accelerometer weighs approximately 5 g and has a theoretical sensitivity of 125 mV/g in the frequency range 200-800 Hz. The basic design allows for easy modification of sensitivity and resonant frequency. This transducer has been effective in detecting sounds associated with turbulent blood flow in partially occluded coronary arteries.

Adult↗
PubMed1993

Hypothalamic versus pituitary stimulation of luteinizing hormone secretion in the prepubertal female lamb.

Glutamate and aspartate have been hypothesized to function as neurotransmitters in the regulation of the gonadotropin-releasing hormone (GnRH) neurosecretory system. We, therefore, determined if hypothalamic stimulation of luteinizing hormone (LH) secretion in the intact prepubertal female lamb could be achieved by intravenous injection of N-methyl-D,L-aspartate (NMA), a glutamate agonist. A pilot study determined a dose of NMA that would induce physiologic pulses of LH (GnRH). Subsequently, we compared the ability of NMA with exogenous GnRH to induce ovulation in the prepubertal lamb when administered chronically. Eighteen prepubertal lambs (21 weeks of age, 34.2 +/- 1.5 kg body weight) were treated intravenously with either NMA (2 mg/kg, n = 6) or GnRH (68 ng/injection or approximately 2 ng/kg, n = 6) for 3 days, every 2 h on day 1 and every 1 h on days 2 and 3, or received no treatment (controls, n = 6). Gonadotropin surges were detected only in GnRH-treated lambs (5/6 lambs, onset = 54.0 +/- 4.5 h from the start of study, mean +/- SE). Compared to 83% of GnRH injections inducing LH pulses, only 47% of NMA injections induced LH pulses. Because each injection of NMA did not induce a pulse of LH, a second experiment was performed in an attempt to optimize the LH response to NMA. Ten prepubertal lambs (25 weeks of age) were injected every 2 h for 24 h with higher doses of NMA, either 4 mg/kg (n = 5) or 16 mg/kg (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Serum bioactive luteinizing and follicle-stimulating hormone concentrations in girls increase during puberty.

FSH plays an essential role in folliculogenesis and ovarian growth. However, cross-sectional studies have not shown an increase in bioactive FSH (B-FSH) during puberty. To eliminate intersubject variability, we used a longitudinal design and tested the hypothesis that B-FSH increases during puberty. Thirty normal, healthy girls were enrolled in a longitudinal study from pubertal stages I to IV. The subjects were evaluated at 6-mo intervals; each visit consisted of pubertal staging, bone age determination by x-ray, measurements of serum immunoreactive FSH (I-FSH) and B-FSH (n = 14) or immunoreactive LH (I-LH) and bioactive LH (B-LH) (n = 18), and adrenal and ovarian steroids. All girls had clinical and hormonal characteristics of puberty. Both I-FSH and B-FSH levels were relatively elevated before puberty, whereas serum I-LH and B-LH were low. From pubertal stages I to III, there was a modest yet significant rise in serum I-FSH (p < 0.001) and serum B-FSH (p < 0.01). Serum I-LH and B-LH concentrations showed the expected increases with puberty (p < 0.001), with serum B-LH concentrations exhibiting a greater rise than I-LH (p < 0.001). Our results demonstrate that serum B-FSH and I-FSH increase during puberty. Relatively elevated B-FSH concentrations from early to midpuberty may be an important factor for ovarian growth while circulating LH and estrogen are still low. As puberty progresses, the continued and selective increase in LH induces a rise in estradiol and ultimately leads to ovulation.

Adolescent↗
PubMed1993

Pulsatile administration of gonadotropin-releasing hormone does not alter the follicle-stimulating hormone (FSH) isoform distribution pattern of pituitary or circulating FSH in nutritionally growth-restricted ovariectomized lambs.

The experimental induction of puberty by GnRH administration to prepubertal lambs increases serum bioactive FSH (B-FSH) as measured in the rat Sertoli cell aromatase induction bioassay. Serum immunoreactive FSH (I-FSH) levels are unchanged. The increase in serum B-FSH is associated with an increase in the proportion of less acidic and more biopotent FSH serum isoforms. However, it is unknown if this effect of GnRH on serum FSH microheterogeneity is direct or mediated by gonadal factors. We have used the nutritionally growth-restricted ovariectomized lamb as a model of the neuroendocrine regulation of FSH isoform microheterogeneity. With this model, the hypothalamic-pituitary component of the neuroendocrine axis may be isolated from gonadal factors. In the present study, using the nutritionally growth-restricted ovariectomized lamb as a model, we investigated the role of GnRH on the regulation of FSH microheterogeneity. Specifically, we tested the hypothesis that GnRH increases the proportion of the less acidic (more biopotent) serum FSH isoforms. As an in vitro correlate, we investigated the effect of GnRH on gonadotropin secretion and FSH isoform distribution in ovine pituitary explant cultures. Seven ovariectomized nutritionally restricted lambs were administered GnRH (i.v., 2 ng/kg) for 36 h (at 2-h intervals for 24 h, then hourly for the final 12 h). Six others served as controls. Blood samples were withdrawn at 12-min intervals during the last 4 h for the measurement of serum immunoactive LH (I-LH) and I-FSH. Pituitary homogenates and serum from four animals from each group were individually chromatofocused, and the FSH isoform distribution patterns were determined. Pulsatile administration of GnRH to nutritionally growth-restricted lambs increased circulating I-LH concentrations from 0.6 +/- 1.0 to 5.9 +/- 3.1 ng/ml (P < 0.01), but did not significantly change circulating I-FSH (4.9 +/- 1.8 vs. 11.5 +/- 4.2 ng/ml) nor B-FSH concentrations (3.9 +/- 1.2 vs. 5.7 +/- 1.5 ng/ml). The pituitary content of I-FSH, B-FSH, and I-LH were unchanged. Neither serum nor pituitary FSH isoform distribution patterns were altered by pulsatile GnRH administration. However, compared to the pituitary FSH isoforms, a higher percentage of circulating FSH isoforms eluted in the salt peak of both groups of lambs. Similar to the in vivo studies, in vitro, GnRH increased the release of I-LH, as well as I-FSH, from pituitary explants, but did not significantly change the FSH isoform distribution in either the pituitary explant or media.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1993

Bioactivity of human growth hormone in serum: validation of an in vitro bioassay.

GH, in clinical practice, is determined by RIA, but RIA estimates may not accurately reflect serum GH bioactivity. The available measures of GH bioactivity lack either sensitivity, specificity, or a physiologically relevant end point. The objective of this research was to develop a physiologically relevant GH bioassay which would not only measure the bioactivity of purified GH preparations, but would also have sufficient sensitivity to measure GH bioactivity in human serum. The method consisted of incubating murine 3T3-F442A adipocytes in serum-free medium containing BSA, 14C-glucose, and increasing concentrations of GH or test materials for 24 h, followed by measurement of conversion of glucose to lipid. Interference by nonspecific serum factors was reduced by the addition of 10 micrograms/liter insulin, 25 nM dexamethasone, and 37 nM estradiol to the medium. In the presence of 10 micrograms/liter insulin, 50 micrograms/liter insulin-like growth factor-1 did not alter the ability of GH to suppress lipid accumulation. Epinephrine and glucagon could suppress lipid accumulation but only at concentrations greatly in excess of the physiological range in serum. Twenty two thousand dalton hGH produced dose-dependent suppression of lipid accumulation which was linear between 0.625 and 10 micrograms/liter (r = 0.926; P = 0.0001) with a half-maximal response of 3.0 +/- 0.2 micrograms/liter (n = six experiments). The intra- and interassay coefficients of variation were 7% and 19%, respectively. The assay was specific for GH since addition of human PRL produced suppression of lipid accumulation only at concentrations where contamination of the preparation by GH became a significant factor. ACTH also suppressed lipid accumulation but only at doses of 1000 micrograms/liter or greater. Human placental lactogen and hLH, hFSH, and hTSH did not cross-react with GH in this assay. Addition of human serum did not alter the slope of ED50 of the GH dose-response curve. Pools of serum from prepubertal and pubertal boys and girls, subjects treated with arginine or insulin, a diabetic girl, and a boy with gigantism who had a serum GH content of 80 micrograms/liter by RIA and 40 micrograms/liter by bioassay, produced dose response curves parallel to that of the GH standard curve. Serum from patients with hypopituitarism did not produce significant suppression of lipid accumulation in any assay. Recovery of 5 micrograms/liter GH added to human serum was 94%. Twenty thousand dalton GH also suppressed lipid accumulation in this assay, but was 2-fold less potent than 22,000 dalton GH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1993

Serum bioactive gonadotropins during male puberty: a longitudinal study.

To evaluate the relative changes in serum bioactive (B) and immunoreactive (I) plasma gonadotropin concentrations during pubertal maturation, 28 healthy boys were enrolled at Tanner stage I and followed at 6-month intervals until achievement of Tanner stage V of pubertal maturation. At each visit, a careful interview, complete physical examination, sexual maturation staging, and bone age x-ray study were done, and a blood sample was obtained. Serum concentrations of PRL, dehydroepiandrosterone, and its sulfate, delta 4-androstenedione, estrone, estradiol, and testosterone (T) were determined by RIA. Samples from 20 boys were assayed for I-LH by RIA and for B-LH by the rat interstitial cell testosterone production assay, using 2 standards [Second International Reference Preparation-Human Menopausal Gonadotropin (2nd IRP-hMG) and LER 960]. Samples from 11 boys (3 from LH group and 8 others) were assayed for I-FSH by RIA and B-FSH by the rat Sertoli cell aromatase induction assay. The results were analyzed by regression analysis for B and I LH and FSH by Tanner stages of puberty, and by correlation of B to I LH and FSH as well as B and I LH and FSH to T. The results from both LH standards correlated well to each other (r = 0.967 and 0.882 for B- and I-LH, respectively), and the data are presented for 2nd IRP-hMG standard. In both groups of boys serum T concentrations increased progressively with pubertal development (P < 0.001). The boys bone age, testicular volume, serum T, dehydroepiandrosterone sulfate, dehydroepiandrosterone, delta 4-androstenedione, estrone concentrations correlated well with pubertal maturation, similar to previously published data and indicate that this group of boys had progressed through puberty in the expected normal manner. Mean serum I-LH concentrations increased progressively from Tanner stage I to V of puberty (P < 0.001), and serum B-LH exceeded the increase in serum I-LH levels. Mean serum I-LH concentrations were 2.0 +/- 0.1, 2.9 +/- 0.2, 4.7 +/- 0.4, 6.7 +/- 0.7, and 10.4 +/- 2.0 IU/L 2nd IRP-hMG whereas mean serum B-LH concentrations were 0.8 +/- 0.1, 2.2 +/- 0.2, 5.9 +/- 0.2, 10.3 +/- 1.2, and 22.3 +/- 3.8 IU/L 2nd IRP-hMG for Tanner stages I-V of puberty, respectively. This resulted in a progressive increase of LH B/I ratio with advancing pubertal maturation (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗
PubMed1993

Luteinizing hormone pulse characteristics in early pubertal boys are the same whether measured by radioimmuno- or immunofluorometric assay.

We tested the hypothesis that the improved sensitivity of immunofluorometric (IFMA) assays will lead to an increase in the number of detectable LH pulses compared to RIA in early pubertal boys, in whom LH secretion is low. To test this hypothesis we determined plasma LH concentrations in six pubertal boys (bone age, 12-16 yr) by IFMA and compared the results to RIA data reported previously. Each boy was given an infusion of saline, followed 1 week later by an infusion of testosterone (T; 960 nmol/h) for 33 h starting at 1000 h. Starting at 1200 h, blood was obtained every 15 min for LH determinations (RIA and IFMA) and every 30 min for T measurements. At the end of both studies, responses to GnRH (250 ng/kg) were assessed. The assay sensitivities for LH by RIA and IFMA (Delfia hLH Spec Pharmacia Diagnostics ENI, Columbia, MA) were 1.0 and 0.05 IU/L, respectively. LH pulses were identified by three independent pulse detection programs: Detect, Cluster, and Kushler-Brown. The correlation for LH values as measured by RIA and IFMA was highly significant (r = 0.81). There was a poor correlation between LH values determined by IFMA and RIA when LH values within 4 times the SD of each assay sensitivity were compared (r = 0.08; P = NS). T infusion suppressed LH pulse frequency by 40% and 66%, as determined by RIA and IFMA, respectively (P = NS). Using the Detect program, during the complete study in all 6 boys, 117 pulses of LH were identified by RIA and 93 by IFMA (79% ratio of detection IFMA/RIA). During saline infusion there were 73 vs. 69 LH pulses (94%), while during T infusion there were 24 vs. 44 LH pulses (55%), as detected by IFMA vs. RIA, respectively. Administration of naloxone did not accelerate LH pulse frequency during T infusion, as determined by either method. Changes in pituitary responses to exogenous GnRH also showed similar trends of augmentation by T infusion by both methods. We conclude that the use of IFMA does not lead to the anticipated increase in the detectability of LH pulsatility. Actually, fewer LH pulses were identified by IFMA in this group of boys. We speculate that this is due to the increased specificity of the IFMA assay. More significant was the finding that the physiological interpretation of the effects of T and naloxone on LH pulse frequency and responses to GnRH did not change whether LH was measured by RIA or IFMA.

Adolescent↗
PubMed1992

Effect of nutritional repletion on pituitary and serum follicle-stimulating hormone isoform distribution in growth-retarded lambs.

Using nutritionally restricted ovariectomized lambs, we tested the hypothesis that nutritionally regulated endogenous increases in GnRH secretion (as assessed by LH pulsatility) not only alter the quantity of FSH present in the pituitary and serum, but also alter the pituitary and serum FSH isoform distribution. Eleven lambs were nutritionally restricted from weaning and ovariectomized at 12 wk of age. Beginning at 56 wk, 6 were fed ad libitum for 14 days, and the other 5 were continued on the restricted diet. Jugular blood samples were collected frequently (12-min interval) for 4 h prior to pituitary removal. Immunoreactive ovine LH (I-oLH) and immunoreactive ovine FSH (I-oFSH) concentrations were measured in sera and pituitary extracts. Bioactive (B) oFSH and I-oFSH isoform distribution patterns were determined in serum pools and pituitary extracts. Ad libitum feeding increased I-oLH pulsatility and mean concentrations of pituitary and serum I-oFSH and B-oFSH. The I-oFSH isoform distribution patterns in the pituitaries from the nutritionally restricted animals were not different from those of repleted lambs; in both, the predominant FSH peak eluted in the pH range of 3.5-5.6. A similar predominance of I-oFSH isoforms was also evident in the serum of ad libitum-fed animals. This predominance was not demonstrable in 3 of the restricted-fed animals due to low circulating concentrations of FSH (less than 2.5 ng/ml). Subsequent studies, utilizing serum from 4 additional restricted-fed lambs with circulating I-oFSH concentrations in the range of 4-14 ng/ml (but no detectable LH pulses) revealed similar predominance of oFSH isoforms in the pH 3.5-5.6 range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Oral clonidine pretreatment for haemodynamic stability during craniotomy.

We have studied the effect of clonidine pretreatment on cardiovascular responses to various stimuli during craniotomy. Fifty-eight patients (ASA Class I-II), scheduled for supratentorial surgery, were randomly given either oral clonidine, mean dose 3.6 micrograms/kg (n = 28), or oral diazepam, 0.2 mg/kg (n = 30), ninety to one hundred minutes before surgery. Anaesthesia was induced with thiopentone and maintained with nitrous oxide:oxygen, pentazocine and halothane. Pancuronium was used as a neuromuscular blocker. Mean arterial pressure and heart rate were recorded before and after several stimuli. In the clonidine group hypertensive response was significantly less on laryngoscopy (6.5% increases versus 11.2% in the diazepam group), intubation (9.2% versus 16.5%), Mayfield clamp application (14.5% versus 29.91%) and after skin infiltration with lignocaine-adrenaline solution (2.95% versus 5.42%). Heart rate response to laryngoscopy, intubation and skin infiltration was also significantly attenuated in the clonidine group. The sleep dose of thiopentone was smaller in patients pretreated with clonidine. Patients in the diazepam group required more medical intervention. No adverse effect occurred in any patient.

Administration, Oral↗
PubMed1992

Progesterone blocks the estradiol-induced gonadotropin discharge in the ewe by inhibiting the surge of gonadotropin-releasing hormone.

Previous studies indicate an elevation of circulating progesterone blocks the positive feedback effect of a rise in circulating estradiol. This explains the absence of gonadotropin surges in the luteal phase of the menstrual or estrous cycle despite occasional rises in circulating estradiol to a concentration sufficient for surge induction. Recent studies demonstrate estradiol initiates the LH surge in sheep by inducing a large surge of GnRH secretion, measurable in the hypophyseal portal vasculature. We tested the hypothesis that progesterone blocks the estradiol-induced surge of LH and FSH in sheep by preventing this GnRH surge. Adult Suffolk ewes were ovariectomized, treated with Silastic implants to produce and maintain midluteal phase concentrations of circulating estradiol and progesterone, and an apparatus was surgically installed for sampling of pituitary portal blood. One week later the ewes were allocated to two groups: a surge-induction group (n = 5) in which the progesterone implants were removed to simulate luteolysis, and a surge-block group (n = 5) subjected to a sham implant removal such that the elevation in progesterone was maintained. Sixteen hours after progesterone-implant removal (or sham removal), all animals were treated with additional estradiol implants to produce a rise in circulating estradiol as seen in the follicular phase of the estrous cycle. Hourly samples of pituitary portal and jugular blood were obtained for 24 h, spanning the time of the expected hormone surges, after which an iv bolus of GnRH was injected to test for pituitary responsiveness to the releasing hormone. All animals in the surge-induction group exhibited vigorous surges of GnRH, LH, and FSH, but failed to show a rise in gonadotropin secretion in response to the GnRH challenge given within hours of termination of the gonadotropin surges. The surges of GnRH, LH, and FSH were blocked in all animals in which elevated levels of progesterone were maintained. These animals in the surge-block group, however, did secrete LH in response to the GnRH challenge. We conclude progesterone blocks the estradiol-induced gonadotropin discharge in the ewe by acting centrally to inhibit the surge of GnRH secreted into the hypophyseal portal vasculature.

Animals↗
PubMed1992

Circulating bioactive follicle-stimulating hormone and less acidic follicle-stimulating hormone isoforms increase during experimental induction of puberty in the female lamb.

The pubertal process with its multifaceted neuroendocrine control provides an excellent model for the study of the regulation of FSH heterogeneity. We tested the hypothesis that during the pubertal transition in the female lamb 1) an increase in both pituitary and circulating bioactive FSH concentrations occur and 2) that the increase in bioactivity is associated with a change in the distribution pattern of both pituitary and circulating FSH isoforms. Pituitary and serum immunoreactive (I), and bioactive (B, Sertoli cell bioassay) FSH concentrations were measured in six prepubertal lambs (18 +/- 1 weeks, 29.9 +/- 2.8 kg body weight; mean +/- SE) and compared to those of six others (24.2 +/- 2.2 weeks of age, 41.4 +/- 2.5 kg body weight) during the pubertal transition period. Puberty was synchronized by pulsatile iv administration of GnRH (2 ng/kg every 2 h for 24 h and then at hourly intervals for the next 12 h) in a manner mimicking the I-LH pulse patterns observed during the natural transition to adulthood. Blood samples were collected at 12-min intervals for 4 h from both groups of lambs; for the pubertal group this included the final 32-36 h of GnRH administration. At the end of the study, a 25 ml volume of peripheral blood was collected from both prepubertal and pubertal females for the determination of serum FSH distribution patterns; the lambs were then euthanised, and pituitaries were removed for determination of pituitary hormone content and FSH isoform distribution patterns. In addition, the distribution pattern of I-FSH isoforms in the pituitary and serum from both groups of lambs were compared. The pubertal stages of all lambs were verified by measuring the size of follicles, the circulating concentrations of estradiol (E2) and inhibin, and the I-LH pulse patterns. Prepubertal lambs had low frequency I-LH pulses, small (2-3 mm) size ovarian follicles and low circulating concentrations of E2 (4.1 +/- 0.4 pg/ml) and inhibin (38.0 +/- 2.9 U/ml WHO). By contrast, all the pubertal lambs had hourly I-LH pulse frequency (induced with exogenous GnRH), a large (5-6 mm) follicle (in one lamb a 4-mm follicle), follicular phase levels of E2 (7.1 +/- 0.8 pg/ml), and higher concentrations of inhibin (53.2 +/- 3.1 U/ml).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Follicle-stimulating hormone signal transduction: role of carbohydrate in aromatase induction in immature rat Sertoli cells.

Receptor activated adenylate cyclase acts as a major transmembrane signalling system. It is widely accepted that upon binding to its receptor, follicle-stimulating hormone (FSH) activates the cAMP-dependent pathway which in turn mediates FSH-induced estradiol production in Sertoli cells. Studies utilizing several chemically derived variants of FSH have demonstrated that these variants bind to the FSH receptors with equal avidity but differ in their ability to activate cAMP-dependent pathways. Since cAMP is believed to be the second messenger responsible for FSH signal transduction, we tested two hypotheses: (1) that the effects of different oFSH variants on cAMP production and aromatase induction (as measured by estradiol production) would be in parallel; and (2) that deglycosylated ovine FSH (DG-oFSH) would antagonize the ability of intact oFSH to stimulate aromatase induction, similar to its reported antagonistic effect on cAMP production. Immature rat (7- to 10-day-old) Sertoli cells were cultured and the effects of several different oFSH variants on cAMP production and/or aromatase induction were tested. The variants tested were native oFSH, DG-oFSH, asialo oFSH (AS-oFSH), a recombinant of intact LH alpha and FSH beta (alpha + beta) and a recombinant of deglycosylated LH alpha and intact FSH beta (DG alpha + beta). Both native oFSH and alpha + beta recombinant at relatively large doses (10 ng) elicited a significant increase in extracellular cAMP accumulation as well as total cAMP production. In contrast, DG-oFSH did not produce an increase in cAMP even at 10-fold higher doses than native oFSH. Intracellular cAMP concentrations did not increase following stimulation with native oFSH, DG-oFSH or DG alpha + beta. In contrast to the divergent effects of oFSH and DG-oFSH on cAMP production all variants of oFSH stimulated estradiol production from Sertoli cells albeit with varying potencies. The sensitivity (minimal effective dose) and ED50 (dose at which half maximal response is achieved) of the estradiol (E2) response curve to increasing concentrations of native oFSH were 0.025 +/- 0.01 and 0.33 +/- 0.05 ng, respectively. Asialo-oFSH (AS-oFSH) increased E2 production with a potency (comparative dose required for effect) similar to that of native oFSH.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Sonographic evaluation of operability of malignant cervical lymph nodes.

Infiltration of the carotid artery by malignant cervical nodes is considered to be a contraindication for radical neck dissection in many centers. Clinical examination alone is unlikely to provide information on the fixity of nodes to the carotid artery. We studied the role of ultrasonography as an adjunct to clinical examination in screening patients for neck dissection. Twenty-seven patients with clinical neck node metastasis were chosen for ultrasonography. All of them had surgery and the findings were correlated. The findings revealed that this procedure is effective in delineating involvement of carotid artery by neck nodes and in identifying false-positive and false-negative cases. Since the sample of patients studied was small, the study is continuing in order to accrue a larger sample.

Adolescent↗
PubMed1991

Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: circulating levels of gonadotropins, their common alpha-subunit and free testosterone, and discrepancy between immunological and biological activities of circulating follicle-stimulating hormone.

The recent availability of both cordocentesis, a low risk and effective technique for fetal blood sampling, and ultrasensitive/highly specific two-site immunofluorometric assays (IFMA) for pituitary and chorionic glycoprotein hormone (I-LH, I-FSH, and I-CG) measurement prompted us to study the maturation of hypothalamic-pituitary-gonadal function in 114 normal human fetuses (49 females and 65 males) from 17-40 weeks gestation. The subjects were selected from 216 consecutive cordocenteses carried out for rapid karyotyping and diagnosis of fetal infection or hematological disorders. In addition, FSH bioactivity (B-FSH) was measured by rat Sertoli cell aromatase induction assay, glycoprotein hormone alpha-subunit (alpha-SU) by RIA, and circulating free testosterone (fT) by direct analog technique. No significant cross-reactions were recorded in the different measurement methods. In particular, alpha-SU did not interfere in any IFMA, and CG cross-reactivity in LH IFMA was 0.5%. Circulating I-LH, I-FSH, and B-FSH levels at 17-24 weeks gestation were significantly higher in female than in male fetuses (I-LH, 48 +/- 4 vs. 6.3 +/- 0.7 U/L; I-FSH, 35 +/- 2 vs. 0.7 +/- 0.1 U/L; B-FSH, 131 +/- 17 vs. 43.4 +/- 5.4 U/L). During the last weeks of gestation, a significant decrease in I-LH and I-FSH levels was seen in both female and male fetuses (I-LH, 0.24 +/- 0.05 and 1.0 +/- 0.3 U/L; I-FSH, 0.45 +/- 0.1 and 0.5 +/- 0.1 U/L), while serum B-FSH remained elevated, but the previously recorded difference between sexes disappeared (54.3 +/- 7.2 and 58.7 +/- 7.3 U/L). Circulating I-CG and alpha-SU levels at midgestation were elevated in both female and male fetuses (I-CG, 117 +/- 29 and 191 +/- 44 U/L; alpha-SU, 143 +/- 16 and 105 +/- 9 micrograms/L, respectively) and decreased thereafter (I-CG, 42 +/- 9 and 26 +/- 6 U/L; alpha-SU, 60 +/- 15 and 37 +/- 6 micrograms/L). Serum fT levels at midgestation were significantly lower in females than in males (4.3 +/- 0.9 vs. 10.0 +/- 0.8 pmol/L) and increased until term, when the difference between sexes disappeared (16.2 +/- 1.8 vs. 17.6 +/- 1.6 pmol/L).(ABSTRACT TRUNCATED AT 400 WORDS)

Embryonic and Fetal Development↗
PubMed1991

Metabolic clearance of human follicle-stimulating hormone assessed by radioimmunoassay, immunoradiometric assay, and in vitro Sertoli cell bioassay.

We measured the equilibrium MCR of purified human FSH via continuous infusion and its half-life by bolus injection in gonadotropin-deficient men. Serum FSH concentrations were determined by RIA, immunoradiometric assay, and an in vitro FSH bioassay (rat Sertoli cell). At steady state, the MCR of FSH averaged 5.4 +/- 0.4 mL/min.m2, which was not statistically different in the three assays at the three different infusion rates. The half-life of FSH after bolus injection averaged 274 +/- 45 min (4.6 +/- 0.75 h) when analyzed as a single exponential, and 1.8 and 10 h for biexponential kinetics. The distribution volume of FSH was 3.1 L (immunoradiometric assay) and 2.1 L (bioassay). In summary, the MCR of human FSH is invariant across a range of physiological gonadotropin concentrations and quantitatively similar in three different immunological/biological assays. These results support the hypothesis that removal of circulating FSH molecules proceeds in parallel for immunoreactive and biologically active glycoprotein hormone.

Adult↗