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Biomedical subjects

C Faiman

Publications and source records attributed to C Faiman.

At least 37 records · Page 2Linked to original sources

Control of gonadotropin secretion in the ovine fetus. IV. Male-specific entrainment of the hypothalamic control of luteinizing hormone secretion by testosterone in the female ovine fetus.

The role of testosterone (T) in the sex-specific entrainment of hypothalamic LH regulation was studied in five castrate and four sham-castrate chronically catheterized female fetuses androgenized by the prior administration of T cypionate (200 mg, im, every 2 weeks) to pregnant ewes from 30-86 days gestation (term = 147 days). Eight female and three male castrate fetuses served as controls. After a 2-week washout period all fetuses were operated upon in utero between 106-116 days and were studied longitudinally over a 2- to 35-day period. LH pulsatility was determined from blood samples obtained every 15 min over a standard 3-h observation period and assayed for LH by RIA (NIH LH-S16 standard). LH pulse frequency in the castrate androgenized females (41 pulses in 19 observation periods; 1 pulse/1.4 h) was significantly higher than that in non-androgenized female controls (18 pulses in 28 observation periods; 1 pulse/4.7 h observation), but was similar to that in castrate males (23 pulses in 28 observation periods; 1 pulse/1.3 h). Furthermore, LH pulse frequency in the sham castrate androgenized females (26 pulses in 13 observation periods; 1 pulse/1.5 h) was comparable to that in castrate androgenized females as well as that in castrate males. The enhanced LH pulsatility in androgenized female fetuses strongly suggests that T exposure between 30-86 days results in male-specific entrainment of hypothalamic LH regulation. Moreover, the comparable enhancement of LH pulse frequency in both sham castrate and castrate androgenized female groups suggests that in the T-exposed fetus T withdrawal alone is sufficient to result in enhanced LH pulsatility. These findings strongly suggest that T of fetal testicular origin results in male-specific entrainment of hypothalamic function and may be an important feature of male neural organization in this species.

Animals↗

Prolactin and sexual dysfunction in women.

Serum prolactin levels were measured in 48 consecutive sexually dysfunctional women who presented to a sexuality clinic. The prevalence of hyperprolactinemia and mean prolactin level of this group were compared to a control group (blood donor volunteers) of 93 women. One woman in the study group (2.1%) was hyperprolactinemic (serum prolactin greater than 15 micrograms/L). However, the differences in both prevalence of hyperprolactinemia and mean prolactin levels, between groups, were not statistically significant. Neither were differences found in mean prolactin levels among subgroups of women in different diagnostic categories and in those with single vs. multiple diagnoses. Nonetheless, because hyperprolactinemia is readily treatable, we would recommend prolactin determinations in sexually dysfunctional women, particularly in those with associated reproductive irregularity or in whom organic etiology is clinically suspect.

Adolescent↗

Hypothalamo-pituitary portal development in the ovine fetus.

The ontogeny of the hypothalamo-pituitary portal system was studied in six ovine fetuses, 48-67 days of gestation (term = 147 days) after infusion of the vascular system with a silicone rubber compound. In all of these fetuses, a marked orange blush of silicone rubber could be seen, under the dissecting microscope, extending down the stalk from the hypothalamus to the pituitary. On microscopic examination, extensive and well-developed capillary connections between the median eminence, the pituitary stalk, and pituitary gland were seen in all fetuses. In an additional fetus, aged 45 days, which was not perfused with silicone rubber, portal capillary loops had penetrated the median eminence. These findings suggest that, in the ovine fetus, hypothalamic releasing factors can be transported directly via a portal vascular route to the pituitary gland as early as 45 days of gestation.

Animals↗

Control of gonadotropin secretion in the ovine fetus. II. A sex difference in pulsatile luteinizing hormone secretion after castration.

Gonadal involvement in the control of fetal LH secretion was examined by studying LH pulsatility in 12 chronically catheterized male (9 castrate and 3 sham-control) and 12 female (8 castrate and 4 sham-control) ovine fetuses operated upon in utero at 106-116 days gestation (term = 147 days). Fetuses were studied longitudinally over a 2- to 30-day period in castrates and over a 2- to 37-day period in controls. LH pulsatility was determined from blood samples obtained every 15 min over a standard 3-h observation period and assayed for LH by RIA (NIH LH S16 standard). In female fetuses there was no significant difference in LH pulse frequency between castrates (25 pulses in 32 periods; 1 pulse/3.8 h of observation) compared to controls (15 pulses in 15 periods; 1 pulse/3.0 h). LH pulse frequency was similar in the sham-castrate males (11 pulses in 17 periods; 1 pulse/4.6 h). In contrast, LH pulse frequency was significantly higher in the castrate male group (90 pulses in 42 periods; 1 pulse/1.4 h) compared to that in each of the other 3 groups (P less than 0.005). LH pulse frequency did not vary with gestational age in castrate and control females or in control males. In castrate males, however, LH pulse frequency declined significantly (P less than 0.005) with advancing gestation from 80 pulses in 32 periods (1 pulse/1.2 h) before 130 days compared to 10 pulses in 10 periods (1 pulse/3.0 h) after 130 days. Thus, LH pulse frequency was indistinguishable in castrate vs. eugonadal males after 130 days. The absence of a castration effect on LH pulsatility in male fetuses older than 130 days was confirmed in an additional group of 8 male fetuses (5 castrate and 3 sham-controls) operated upon at 121-130 days gestation and studied over a 2- to 20-day period. Overall, LH pulse amplitude was similar in male [4.7 +/- 0.5 ng/ml (+/- SE)] and female (3.9 +/- 0.5 ng/ml) fetuses and did not vary as a function of gonadal status or gestational age. The postcastration increment in LH pulse frequency in the castrate male fetus from 108-130 days gestation delineates a role of the fetal testis in feedback regulation of LH secretion at this stage of development. The absence of a postcastration rise in LH pulse frequency in the castrate female indicates that the fetal ovary does not play a similar role.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Role of endogenous opiates in the modulation of gonadotropin secretion in infant monkeys (Macaca mulatta): effects of naltrexone.

A potential inhibitory role of endogenous opioids in the gonadotropin decline from infancy to the prepubertal period in primates was assessed by examining the effect of the specific opioid antagonist naltrexone on gonadotropin levels in infant rhesus monkeys. Paradoxically, both chronic administration of naltrexone to neonatally castrate males as well as acute administration of graded doses to intact infant females resulted in gonadotropin suppression compared to appropriate vehicle-treated controls. Thus, naltrexone behaves as a gonadotropin secretory antagonist in infant monkeys and cannot be used to unmask a putative inhibitory mechanism involving endogenous opiates.

Animals↗

Effects of long-term testosterone exposure on ovarian function and morphology in the rhesus monkey.

This study was aimed at developing a model in the rhesus monkey for the human gynecologic disorder termed the polycystic ovary syndrome (PCOS). The effects of chronic constant androgen exposure upon quantitative ovarian morphology and ovulatory function were examined. Twenty-five normally cycling females, aged 4-12 yr and weighing 3.3-8.2 kg, were enrolled in the study in random fashion. Seventeen animals were implanted subcutaneously (s.c.) with 10 or 25 mg testosterone-filled silastic tubing so as to maintain steady serum levels of testosterone averaging 80 ng/dl (low-dose group, n = 8) and 115 ng/dl (high-dose group, n = 9) for 13-16 months. Eight animals served as controls (sham implants); in these, mean serum testosterone levels averaged 24 ng/dl. No effect of androgen treatment was observed on ovulatory function as gauged by periodic luteal phase progesterone determinations and the presence of a fresh corpus luteum at laparoscopy. Menstrual cycle frequency (number of cycles over number of months of observation) was, however, slightly but significantly (P less than 0.05) reduced in the high-dose (88.9%) vs. the control (96.7%) and low-dose (95.0%) groups. Quantitative morphology, performed by light microscopy on a single ovary obtained from 16 of the 25 animals and read in a blinded fashion, revealed no differences in ovarian weight, capsular width and numbers, size, or proportion of healthy and atretic follicles among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Primary radiotherapy of prolactinomas. Eight- to 15-year follow-up.

Eight women with amenorrhea, galactorrhea, and hyperprolactinemia, of whom six had macroadenomas and two had microadenomas, were treated with conventional (cobalt-60) external radiotherapy, and their progress was monitored for eight to 15 years. Normoprolactinemia was established in five of these patients after two to 13 years (median, nine years). A recurrence was treated surgically in one patient, and stable prolactin values and roentgenographic features have been maintained in two patients. Hypopituitarism has developed in only one patient to date, and no other complications of radiotherapy have been observed. These findings, together with the few previous reports on the long-term effects of radiotherapy on macroprolactinomas, have been compared with the long-term results following surgery or dopamine agonist therapy. The normalization of prolactin values is considerably delayed following radiotherapy compared with the other two therapeutic modalities. However, radiotherapy affords permanent normalization without recurrence in a larger percentage of patients than does surgery and avoids the considerable ongoing cost and inconvenience of daily drug ingestion. The long-term development of hypopituitarism appears to be an acceptably small risk of radiotherapy. Thus, conventional radiotherapy is an attractive treatment option, particularly for macroprolactinomas; adjunctive bromocriptine can be used while awaiting the longer-term benefits of radiotherapy.

Adult↗

Aplasia of nasal cilia with situs inversus, azoospermia and normal sperm flagella: a unique variant of the immotile cilia syndrome.

A 23-year-old man with situs inversus and bronchiectasis was investigated because of azoospermia. Serum levels of testosterone and pituitary gonadotropins were normal. Scrotal exploration revealed no abnormalities of the testes, epididymides or vasa deferentia. Electron microscopy of a testicular biopsy specimen revealed a normal sperm flagellum structure, including the presence of dynein arms but 2 separate biopsies of the nasal mucosa revealed complete ciliary aplasia. This case, which bears a striking resemblance to Young's syndrome (bronchiectasis and azoospermia), represents a unique variant of the immotile cilia syndrome.

Adult↗

Chlorpropamide overdose in renal failure: management with charcoal hemoperfusion.

A potentially lethal chlorpropamide overdose in a patient with chronic renal failure on long-term hemodialysis was treated by two courses of charcoal hemoperfusion. Hemoperfusion shortened the half-life clearance of the drug from a mean value of 93.6 to 3.4 hours. Calculation of the fractional extraction indicated that hemoperfusion reduced the body burden of the drug by 24% and 19% (mean values) during the first and second hours of treatment, respectively. We conclude that charcoal hemoperfusion should be considered a definitive therapeutic option in such cases.

Adult↗

Control of gonadotropin secretion in the ovine fetus: the effects of a specific gonadotropin-releasing hormone antagonist on pulsatile luteinizing hormone secretion.

To demonstrate the dependence of fetal pituitary LH secretion endogenous GnRH, we studied the effects of bolus iv administration of a specific GnRH antagonist analog [GnRH-Ant; (N-acetyl-D-p-chloro-Phe1,2,D-Trp3,D-Arg6,D-Ala10)GnRH] on pulsatile LH release in 10 chronically cannulated ovine fetuses of 104-129 days gestation (term, 147 days). Vehicle alone was given to 13 control fetuses of 107-125 days gestation. Blood samples for LH determination by RIA (NIH LH S16 standard) were taken after injection of either GnRH-Ant (175-300 micrograms dissolved in 1 ml 5% dextrose in water) or vehicle alone for 1.75-5 h. The efficacy of GnRH receptor blockade was then assessed by a bolus iv challenge with 50 micrograms synthetic GnRH. The mean (+/- SEM) observation period per animal was similar for the two groups (3.8 +/- 0.2 h for GnRH-Ant; 3.6 +/- 0.2 h for controls). The frequency of spontaneous pulsatile LH secretion was significantly decreased in the fetuses given GhRH-Ant (2 pulses over 38 h total observation vs. 13 pulses over 47.3 h in control fetuses; P = 0.006). The average interpulse interval was 19.0 h in the GnRH-Ant group compared to 3.6 h in controls. Although the mean pulse amplitude was lower in the GnRH-Ant group (2.8 +/- 1.2 vs. 7.6 +/- 1.1 ng/ml for controls), this difference was not statistically significant (P = 0.065, by one-tailed t test). The mean peak serum LH concentration in response to the GnRH challenge was significantly blunted in the GnRH-Ant group (4.6 +/- 0.8 vs. 20.6 +/- 1.8 ng/ml for controls; P less than 0.001). These results indicate that GnRH-Ant administration causes a virtual cessation of pulsatile LH discharge. As this GnRH-Ant blocks GnRH action at the receptor level, these data demonstrate that pulsatile LH secretion in the ovine fetus is dependent on endogenous GnRH release as early as 104 days gestation.

Animals↗

The role of gonadal steroids in feedback regulation of gonadotropin secretion at different stages of primate development.

The serum gonadotropin response to castration was assessed in 8 foetal, 2 neonatal, 30 juvenile, and 2 adult rhesus monkeys (M. mulatta). In the 30 castrated juvenile monkeys and 8 sham-operated controls, concentrations of oestrone, oestradiol, androstenedione, dihydrotestosterone, testosterone and 17OH-progesterone were measured in 10 ml serum pools before, one month after, and one year after the surgical procedure. Castration during foetal life (83-137 days gestation) was followed within 48-72 h by a significant rise in serum FSH levels in males, but had no effect on the already high levels in females. Similarly, castration of males during the first post-natal month raised serum FSH and LH into the adult castrate range; however, after 3 months of age serum gonadotropin levels again declined to the normal juvenile range in spite of the open feedback loop. Orchiectomy of prepubertal juvenile monkeys (age 3 month-2 8/12 years) had no immediate effect on serum gonadotropins, but was followed by a delayed rise in FSH (at age 2 3/12-4 3/12 years) and LH (at age 2 7/12-4 4/12 years) to adult castrate levels. Orchiectomy of older prepubertal (by serum testosterone) or adult males resulted within a few days in a progressive and sustained rise in serum FSH and a more gradual rise in LH. Prepubertal gonadotropin regulation appeared to be sexually dimorphic, since ovariectomy in juvenile females (age 3 months-1 5/12 years) was followed by generally elevated, if somewhat erratic, serum FSH values, with a secondary rise in both FSH and LH levels at 2-2 1/12 years. In both sexes, prepubertal castration caused a significant and sustained decline in serum concentrations of oestradiol; castrated males also showed a decline in serum testosterone levels. Although prepubertal castration also caused in both sexes a slight decline in serum oestrone, and ovariectomy a decline in serum androstenedione and dihydrotestosterone, these effects were not sustained one year later, and values were not significantly different from sham-operated controls. Taken together, these data lend support to a model of primate sexual maturation in which the primary regulator of gonadotropin secretion in both sexes during the prolonged juvenile phase is central inhibition of the hypothalamic GnRH regulator. However, during foetal and neonatal life, and again following the onset of puberty, the major modulator of gonadotropin secretion becomes sex steroid-mediated feedback inhibition.

Age Factors↗

Insulin and insulin-receptor autoantibodies in children with newly diagnosed IDDM before insulin therapy.

Twenty-nine children, aged 1-15 yr, with newly diagnosed insulin-dependent diabetes mellitus (IDDM) had sera taken before insulin therapy to be examined for the presence of insulin-receptor antibodies by measuring the inhibition of binding of radiolabeled insulin to IM-9 lymphocytes in both whole serum and purified IgG fractions. Groups of children with long-standing IDDM and autoimmune endocrine disease as well as a normal control group were studied. A positive result, defined as binding greater than or equal to 2 SD below the mean zero standard, was found in 3 (10.3%) of the 29 newly diagnosed diabetic patients. As a group, they showed significantly greater binding inhibition than the normal control group for both whole serum and purified IgG (one-tailed t test, P less than .05 and P less than .002, respectively). Insulin autoantibodies were also measured by a sensitive radioimmunoassay technique. A positive result, defined as binding greater than 3 SD above the normal control pooled sera, was found in 9 (37.5%) of 24 of the newly diagnosed IDDM group tested. All 3 subjects positive for insulin-receptor antibodies were also positive for insulin autoantibodies, whereas 6 of the 21 receptor-antibody-negative subjects were positive for insulin autoantibodies (Fisher's exact test, P = .0415). This suggests the possibility that the presence of insulin autoantibodies is a prerequisite for the development of insulin-receptor antibodies, i.e., as an anti-idiotypic response. Insulin-receptor antibodies and insulin autoantibodies may play a currently undefined pathophysiologic role in the development of IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Postpartum disappearance of chorionic gonadotropin from the maternal and neonatal circulations.

The disappearance of chorionic gonadotropin from the circulation was studied in a group of 10 healthy mothers and their offspring following vaginal delivery. Kinetic analysis revealed the following biexponential clearance characteristics: in mothers the rapid half-life component averaged 4.75 +/- 0.58 (SE) hours (n = 6), and the slow half-life component averaged 32.2 +/- 1.35 hours (n = 6); in neonates the respective overall means were 1.32 and 55.2 hours. Total elimination of chorionic gonadotropin (less than 0.005 IU/ml) occurred at a median time of 14 days following birth (range, 8 to 24 days) in mothers and at 1.5 days (range, 0 to 4 days) in neonates.

Chorionic Gonadotropin↗

Pituitary-gonadal function in Klinefelter syndrome before and during puberty.

Serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol were determined at intervals before and during puberty in 40 individuals with Klinefelter syndrome (47,XXY karyotype), of whom 27 had been detected in neonatal cytogenetic screening programs. Prior to the appearance of secondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropin-releasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.

Adolescent↗

Intraadrenal steroid concentrations in man: zonal differences and developmental changes.

Adrenal gland samples from 34 individuals 0-68 yr of age were dissected into four layers of equal thickness parallel to the capsule and the zonal boundaries of the cortex, and were analyzed by RIA for their concentrations of 17OH-progesterone, 11-desoxycortisol, cortisol, progesterone, corticosterone, aldosterone, 17OH-pregnenolone, dehydroepiandrosterone, androstenedione, and testosterone, with DNA content to correct for variations in sample size. Intraadrenal steroid concentrations were 10-1000 times higher than reported serum levels, and varied significantly with age, adrenal weight, and cortical thickness. The concentrations of cortisol,11-desoxycortisol, corticosterone, androstenedione, and testosterone increased with age. Levels of 17OH-pregnenolone, dehydroepiandrosterone, and 17OH-progesterone decreased during infancy in parallel with involution of the adrenal, and then rose again in late childhood and puberty. The concentrations of all steroids, except aldosterone, increased significantly from the outer to the inner layers of cortex. Comparisons of product-substrate ratios suggested that changes in adrenal androgen secretion are induced by shifts in the relative activities of key branch-point steroidogenic enzymes, notably 3 beta-hydroxysteroid dehydrogenase-isomerase and 17,20-desmolase. Since intraadrenal steroid concentrations are in the range of the Michaelis-Menten constant (Km) for these enzymes (10(-6) M) and can be shown in vitro at this concentration to influence relative enzyme activities, these data support the hypothesis that zonal and developmental changes in adrenal androgen secretion relative to that of cortisol are induced by changes in the steroidal micro-environment which in turn are imposed by adrenal growth and the centripetal blood flow through the gland.

17-Hydroxysteroid Dehydrogenases↗

Influence of restraint and ketamine anesthesia on adrenal steroids, progesterone, and gonadotropins in rhesus monkeys.

Changes in gonadotropins, progesterone, cortisol, DHA, and DHAS were monitored in 10 female rhesus monkeys (Days 20-23 of the menstrual cycle) subjected to cage restraint with or without ketamine anesthesia for successive venipunctures. All animals were bled without sedation for 2 hr at 30-min intervals. Then 4 of the animals were anesthetized with ketamine-HCl and bleedings in all animals were continued for an additional 2.5 hr. FSH and progesterone were not appreciably affected by either restraint technique. LH declined steadily for the duration of the bleedings (P less than 0.05). Serum levels of cortisol and the adrenal androgens increased twofold (P less than 0.05). Anesthesia with ketamine had no effect on any of the six variables when compared with saline controls. Cortisol and dehydroepiandrosterone (DHA) levels tended to plateau (P less than 0.01) after 2 hr in both treated and control groups. In contrast, dehydroepiandrosterone sulfate (DHAS) levels increased continuously throughout the entire study period. These data indicate that ketamine anesthesia does not alter endocrine responses to venipuncture when administered following cage restraint of conscious animals. These findings further confirm the difficulties in obtaining estimates of basal levels of hormones which are responsive to stress and suggest that the first sample may provide the best estimate.

Anesthesia↗

An extra-pancreatic direct effect of streptozotocin on the hypothalamo-hypophyseal-testicular axis in the rat.

Streptozotocin induced diabetes mellitus in 4 out of 6 male rats. On the other hand, all 6 drug-injected animals had decreased serum testosterone values. The Leydig cells from 6 control rats and all streptozotocin-injected animals were characterized by moderate numbers of mitochondria, few lipid droplets, and an abundance of smooth surfaced endoplasmic reticulum. Quantitative analysis of numbers of mitochondria and lipid droplets revealed no differences between control and streptozotocin-injected animals. However, there were smaller mitochondria, larger lipid droplets and a trend toward fewer cells with dilated profiles of smooth endoplasmic reticulum in all drug injected animals. These cytological and biochemical findings suggest that diabetes per se had little direct effect on Leydig cell function. However, taken together with previous studies, these observations suggest that streptozotocin may directly affect the hypothalamo-pituitary-testicular axis possibly at the level of LHRH-secreting neurons of the hypothalamus.

Animals↗