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Biomedical subjects

M S Blank

Publications and source records attributed to M S Blank.

At least 19 recordsLinked to original sources
PubMed1994

Endogenous opioids and hypogonadism in human obesity.

Massively obese males often show symptoms of hypogonadism, but the mechanism for this is unclear. Increased endogenous opioid inhibition of the hypothalamic GnRH pulse generator resulting in insufficient stimulation of the pituitary gonadotroph has been proposed as a possible mechanism. If this hypothesis is correct, obese males should be more sensitive to the LH-elevating effects of the opiate antagonist, naloxone, than men of normal weight and gonadal status. This study investigated the etiology of obesity-related hypogonadism by examining luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin-releasing hormone (GnRH) and to infusions of saline or naloxone. Subjects were five obese (201 +/- 14% IBW) and five normal weight (control) (97 +/- 4% IBW) males. Before treatment, obese males had significantly (p < 0.05) lower testosterone levels than control subjects (307 +/- 72 vs. 597 +/- 49 ng/dl), whereas estradiol, androstenedione, and dehydroepiandrosterone levels were not different between the two groups. Both groups showed equivalent elevations in LH (fourfold to sixfold) in response to GnRH stimulation, but obese patients had significantly lower basal (p < 0.05) and GnRH-stimulated (p < 0.01) FSH levels. Infusions of naloxone (but not saline) led to significant (p < 0.01) increases in LH above preinfusion baseline levels (20.5 +/- 2.8% in obese and 28.6 +/- 6.3% in controls). In control subjects, integrated LH levels during naloxone infusion were not significantly elevated above those found during saline infusion, while obese subjects exhibited a 43% augmentation of integrated LH (31.0 +/- 5.3 ng/ml during naloxone vs. 21.7 +/- 1.8 ng/ml during saline, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Luteinizing hormone sensitivity to naloxone in maturing male chimpanzees.

We have systematically investigated the involvement of endogenous opioids in gonadotropin secretion during primate sexual maturation by examining LH/FSH responses to gonadotropin-releasing hormone (GnRH) and changes in LH secretion during infusions of saline or naloxone, an opiate antagonist, in ten male chimpanzees between one and nine years of age. Animals were anesthetized with ketamine (10 mg/kg) and injected or infused IV with GnRH, naloxone or saline. Circulating levels of serum LH were elevated to the same extent (approximately 400%) in response to GnRH (100 micrograms) in animals 1-5 years old (juvenile) and in animals 6-9 years old (pubertal). No differences were noted between the two groups in GnRH-stimulated levels of serum FSH. During treatment with naloxone (0.14 mg/kg bolus followed by 0.2 mg/kg/h maintenance infusion for 3 h), serum LH levels in pubertal animals were significantly (p less than 0.05) elevated by as much as 95% over LH levels found during treatment with saline. Juvenile animals, on the other hand, failed to demonstrate significant increases in serum LH following naloxone at the doses tested. A strong correlation (r = .84) was found between circulating testosterone and serum LH levels during naloxone treatment. These data indicate that opioid inhibition of LH secretion can be reversed by naloxone only when puberty is reached in chimpanzees and suggest an alteration in opioid regulation of GnRH near the time of puberty. The strong correlation between testosterone levels and LH responses to naloxone suggests that steroids may participate in the maturation of opioid control of LH during puberty of nonhuman primates.

Aging↗
PubMed1987

A case of thyroxine thyrotoxicosis.

A 57-year-old woman presented with palpitations, muscle weakness, bilateral proptosis, goiter, and tremor. The thyroxine (T4) level and the free T4 index were increased while the total triiodothyronine (T3) level was normal. Iodine 123 uptake was increased, and a scan revealed an enlarged gland with homogeneous uptake. Repeated studies again revealed an increased T4 level and free T4 index and normal total and free T3 levels. A protirelin test showed a blunted thyrotropin response. Treatment with propylthiouracil was associated with disappearance of symptoms and normal T4 levels, but after 20 months of therapy, hyperthyroidism recurred and the patient was treated with iodine 131. This was an unusual case of T4 toxicosis because the patient was not elderly and was not exposed to iodine-containing compounds or drugs that impair T4-to-T3 conversion. There was no evidence of abnormal thyroid hormone transport or antibodies.

Autoantibodies↗
PubMed1986

Central, stereoselective receptors mediate the acute effects of opiate antagonists on luteinizing hormone secretion.

Although a central site of acute opiate action in regulating luteinizing hormone (LH) secretion has been suggested by the ability of centrally implanted opiate antagonists to increase LH levels, opiate antagonists are lipophilic and could influence the pituitary in situ. Also, the physiological significance of opiate receptor blockade with antagonists rests on the assumed, but untested, stereoselectivity of these receptors. Therefore, a lipophobic quaternized derivative of naltrexone (MRZ 2663-Naltrexone methobromide) and dextro- (+) and levo- (-) stereoisomers of naloxone were used to study the site- and stereoselectivity of gonadotropin responses to opiate antagonists in vivo. Male rats were injected intracerebroventricularly (icv) or intravenously (iv) with the quaternary or tertiary congeners of naltrexone and subcutaneously (sc) with (-) or (+)-naloxone. Rats injected icv with 20 ug of quaternary naltrexone displayed significant increases in serum luteinizing hormone (LH). The onset of the response was rapid with serum LH levels being significantly elevated 15 minutes after the injection and returning to basal levels 30 minutes later. Rats injected iv with 10 mg/kg of quaternary naltrexone failed to show significant LH responses. Rats injected either centrally or periphally with equivalent doses of tertiary naltrexone showed LH responses that were similar to those found in animals injected icv with quaternary naltrexone. As little as 0.5 mg/kg of (-)-naloxone resulted in significant elevations in serum LH that were higher than those elicited by up to 10 mg/kg of (+)-naloxone, indicating that this effect of naloxone is stereoselective. These data support the argument that opioids can acutely modulate LH secretion through actions at stereoselective opioid receptors in the central nervous system.

Animals↗
PubMed1986

Prolactin and blood pressure responses to perphenazine in human subjects: comparison of the oral and intramuscular routes.

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr +/- SD) was significantly shorter (p less than 0.05) for the 5mg IM (1.7 +/- 0.4) than the oral (4.5 +/- 0.6) route. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 +/- 5.69) than the oral (5.12 +/- 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2 mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.

Administration, Oral↗
PubMed1986

Definition of bioactive prolactin pulsations during the menstrual cycle.

Patterns of circulating prolactin bioactivity during three stages of the menstrual cycle were studied in detail in four normally cycling women. Serial blood samples were withdrawn at 10 or 15 min intervals for up to 8 h. Plasma prolaction concentrations were quantitated by a bioassay which is based on the replication of a rat lymphoma cell line (Nb2 node) and by conventional radioimmunoassay. A total of 50-103 samples from each patient was analysed. Using a threshold-based algorithm, definite pulsations of prolactin biological (B) and immunological (I) activity were detected at most stages of the menstrual cycle. The periodicity of these peaks ranges from 1 to 1 1/2 h. However, pulsations were less evident in one subject who had asymptomatic hyperprolactinaemia although circulating prolactin was fully bioactive (mean B:I ratios being 1.02-1.25). B:I ratios in the three normoprolactinaemic women were generally lower, ranging from 0.39 +/- 0.02 to 0.93 +/- 0.03. Elevations in the B:I ratio of normoprolactinaemic women were associated with bioactive peaks; this was not always the case in the hyperprolactinaemic subject. Thus, the lack of symptoms in this hyperprolactinaemic subject could not be due to bioinactive prolactin, but might perhaps be due to the absence of episodic prolactin secretion which would desensitise target organs.

Adult↗
PubMed1986

Bioactivity of serum and pituitary prolactin during the rat estrous cycle.

The availability of a mitogenic bioassay for PRL in which multiple, small samples could be analyzed led us to examine circulating and pituitary PRL bioactivity during the estrous cycle of the rat. Bio- (B) and immuno (I)-activities were compared in individual samples using rat PRL RP-1 standard. B:I ratios ranged between 2.3 and 6.8 for serum and 1.4 and 3.2 for pituitaries. Serum bioactivity increased 24-fold during the surge of PRL on the afternoon of proestrus, whereas pituitary bioactivity decreased almost 5-fold during this time period. Serum B:I ratios were significantly (P less than 0.01) elevated on the day of proestrus (0900-1800 h) compared to those on diestrous day 2. Pituitary B:I ratios ranged from a high of 2.3 +/- 0.3 on diestrous day 2 and 1500 h on proestrus to 1.8 +/- 0.1 on diestrous day 1. Differences between mean B:I ratios of pituitaries obtained at different cycle stages were not statistically significant. Interestingly, serum B and I were not correlated (r = 0.55, 0.68) at the peak of the proestrous PRL surge when pituitary extracts exhibited the highest correlation (r = 0.94). The augmented bioactivity of serum compared to that in pituitaries was not due to a synergistic serum effect. It is likely that the proestrous PRL surge, similar to the preovulatory LH surge, results from secretion of a pool of high biological activity. Since no evidence was found for a lactogen synergist in the circulation, the difference between serum and pituitary bioactivity could reflect an averaging of releasable and nonreleasable pools of PRL with varying degrees of biopotency. That these differences result from postsecretion enhancement of PRL biopotency, possibly due to changes in molecular structure and/or conformation, also cannot be ruled out. PRL biopotency in the circulation of the rat is much higher than that reported for women, perhaps reflecting the physiological relevance of PRL to luteal function in the rat.

Animals↗
PubMed1986

Inhibition of luteinizing hormone release by morphine and endogenous opiates in cultured pituitary cells.

Morphine sulfate was found to have a direct inhibitory effect on both basal and GnRH-stimulated LH release by cultured rat pituitary cells. The inhibitory effect of morphine on LH release was prevented by the opiate antagonist naltrexone, and treatment of cells with naltrexone or beta-endorphin antiserum significantly increased basal LH release. Also, incubation of pituitary cells with CRF caused a significant decrease in basal LH release, an effect that was reversed by naltrexone. Saturable opiate-binding sites were demonstrated in enriched gonadotrophs by [3H]etorphine binding studies. The ability of morphine to inhibit gonadotropin secretion through a direct action on pituitary opiate receptors suggests that long term exposure to exogenous opiates may suppress reproductive function at the hypophyseal level. In addition, the converse effects of CRF and naltrexone or beta-endorphin antiserum on LH release indicate that intrapituitary opioid peptides could exert a paracrine inhibitory action on the gonadotroph.

Animals↗
PubMed1985

Reproductive biology of paraplegics: results of semen collection, testicular biopsy and serum hormone evaluation.

The fertility and urological status of 30 male paraplegics between 20 and 47 years old with lesions between the T2 and L3 levels were examined by studying serum hormone levels (estradiol-17 beta, testosterone, prolactin, and follicle-stimulating and luteinizing hormones), sperm and semen characteristics via testicular biopsy and rectal probe electrostimulation, and urodynamic evaluation. Of the patients 13 had reflexic, 4 hyperreflexic and 13 areflexic bladders. Nine of the 13 patients with reflexic and all 4 with hyperreflexic bladders had a positive external sphincter electromyogram with detrusor-sphincter dyssynergia. When catheters were not used to collect semen during rectal probe electrostimulation, retrograde semen flow into the bladder was the rule. A total of 22 patients could tolerate rectal probe electrostimulation, while 6 who could not were injured at the T12 level or lower. Seminal emissions were obtained from 35 to 42 studies in these 22 patients. Total sperm count was variable; in 22 studies it was greater than 20 million. Progressive motility usually was low; 77 per cent of the patients had less than 20 per cent motility. Of 13 biopsy specimens obtained 6 suggested normal testicular morphology, with tubule atrophy and spermatogenic activity only mildly reduced in 6 of the remaining 7. Serum testosterone and luteinizing hormone values were significantly higher (p less than 0.05) among the paraplegic patients than among intact male volunteers of the same age range. Other serum hormone levels were unchanged. Outcome of rectal probe electrostimulation and biopsy did not relate to the number of years of patient injury. Thus, the principal deterrent to the use of semen collected by rectal probe electrostimulation from paraplegics for artificial insemination resides in a predominantly low sperm motility. Suggestions for improvement of motility include 1) great care to minimize or prevent urinary tract infections, 2) selection of medications for urinary tract care that do not compromise sperm survival and 3) prevention of sperm stagnation in lower tract storage sites, perhaps by use of periodical rectal probe electrostimulation.

Adult↗
PubMed1985

The effects of piracetam in children with dyslexia.

Following previous research which suggests that piracetam improves performance on tasks associated with the left hemisphere, a 12-week, double-blind, placebo-controlled study of developmental dyslexics was conducted. Six study sites treated 257 dyslexic boys between the ages of 8 and 13 years who were significantly below their potential in reading performance. Children were of at least normal intelligence, had normal findings on audiologic, ophthalmologic, neurologic, and physical examination, and were neither educationally deprived nor emotionally disturbed. Piracetam was found to be well tolerated in this study population. Children treated with piracetam showed improvements in reading speed. No other effects on reading were observed. In addition, improvement in auditory sequential short-term memory was observed in those piracetam-treated patients who showed relatively poor memory at baseline. It is suggested that longer term treatment with piracetam may result in additional improvements.

Adolescent↗
PubMed1985

Inhibition of gonadotropin-releasing hormone release as the basis of pituitary-gonadal dysfunction during treatment with 4-aminopyrazolo-(3,4-d)-pyrimidine.

The inhibitor of hepatic lipoprotein release, 4-aminopyrazolo-(3,4-d)-pyrimidine (4-APP), has been shown to reduce testosterone production via impairment of pituitary gonadotropin secretion rather than through decreased cholesterol availability. It was previously shown that serum LH levels were reduced by more than 75% in male rats treated with 4-APP, but pituitary stores of LH and the gonadotropin response to exogenous GnRH were maintained. Also, there was a reduction in pituitary GnRH receptors which was consistent with hypothalamic GnRH deficiency. The present studies were undertaken to examine the mechanism by which 4-APP inhibits GnRH synthesis and/or release. Intact, adult male or 2-week ovariectomized female rats were treated daily with 25 mg/kg 4-APP for 3 days. Both sexes showed lowered basal serum levels of LH and absence of the elevations in serum LH normally elicited by the opiate antagonist, naloxone. In pituitary portal plasma collected from normal male rats, GnRH was significantly elevated by naloxone treatment, confirming that naloxone acted at the level of hypothalamic GnRH release. However, naloxone stimulation of GnRH secretion into portal blood was absent in rats treated with 4-APP. In vitro, the potassium-induced release of GnRH from perifused medial hypothalami was reduced by 60% in 4-APP-treated male rats while hypothalamic GnRH content remained unchanged. These data indicate that 4-APP has an inhibitory effect on the mechanism of GnRH release, and that analysis of its actions should clarify the processes involved in neurohormone secretion.

Adenine↗
PubMed1985

Negative feedback effects of oestradiol-17 beta on luteinizing hormone in female rhesus monkeys under different seasonal conditions.

Suppression of luteinizing hormone (LH) by sc implanted oestradiol-17 beta (E2) pellets was examined in 4 ovariectomized female rhesus monkeys during the breeding season, the non-breeding season and during the transition between the breeding and non-breeding season. Immunoreactive LH was suppressed to 58, 78 and 75% of untreated levels for the respective seasonal conditions. Bioactive LH was suppressed to 29, 49 and 33% of baseline. Bioactive LH (determined by testosterone release from rat interstitial cells) was significantly correlated (r = 0.84) with immunoactive LH from the same samples. It is concluded that E2 treatment of ovariectomized female rhesus monkeys results in suppressed levels of LH, regardless of the time of year.

Animals↗
PubMed1984

Endocrine changes induced by venipuncture in rhesus monkeys.

An animal-worn, remotely activated blood collection device was used to obtain estimates of baseline levels of testosterone (T), growth hormone (GH) and prolactin (PRL) from unrestrained and active male rhesus monkeys. As soon as possible after this baseline period, the males were captured and a final venipuncture sample was obtained. Venipuncture produced elevated GH levels compared to values obtained using the blood collection device, but was without detectable effect upon levels of T and PRL. Cortisol values, available only from a single animal, displayed an increase in response to venipuncture, much like that seen for GH.

Animals↗
PubMed1984

Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats.

The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25-26 days of age, and an Alzet osmotic minipump containing ACTH (1-24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 micrograms of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 +/- 94 vs 443 +/- 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1984

Timing of sexual maturity in female rhesus monkeys (Macaca mulatta) housed outdoors.

A comparison of the age and season at first parturition was made for spring-born female rhesus monkeys and for females born in the fall to mothers who had been laboratory-housed before being transferred outdoors. Females (N = 9) born during the fall had first parturition during the spring and summer, as did all spring-born females (N = 68), and not during the fall as would be predicted if age were the determining factor. A separate analysis of post-menarchial, spring-born females (N = 5) beginning in September at 29 months of age revealed that the ensuing 12 months were characterized by low serum levels of oestradiol (less than 50 pg/ml), progesterone (less than 1.0 ng/ml), LH (less than 7.0 ng/ml), and FSH (less than 5.50 micrograms/ml). First ovulation subsequently occurred in the fall in all subjects at a mean age of 41.9 +/- 0.1 months, and was preceded by significant elevations in basal LH and FSH, coincident in time with the transition of summer to fall (September). Female copulatory behaviour was restricted to the period surrounding first ovulation, beginning some 2 weeks before and ceasing within 3 days after the oestradiol peak. The most rapid gain in weight occurred during the summer months before first ovulation, and was associated with significant elevations in serum GH and prolactin. These data suggest that season may influence the timing of sexual maturation in rhesus monkeys kept outside in such a way that the occurrence of first ovulation is restricted to the fall and winter months.

Animals↗
PubMed1984

Luteinizing hormone and gonadal steroid levels during the menstrual cycle of orangutans.

Serum luteinizing hormone (LH), progesterone, 17 beta-estradiol, and testosterone were measured during a single cycle each of five female orangutans, and urinary LH was measured in four of those cycles. Midcycle peaks in LH and luteal phase elevations in progesterone (5.7-13.8 ng/ml) suggested that the cycles were ovulatory. 17 beta-Estradiol was elevated at midcycle (163-318 pg/ml) and during the luteal phase (56-136 pg/ml) and testosterone was also elevated at midcycle (143-580 pg/ml). These hormone patterns in the orangutans closely resemble those for chimpanzees, gorillas, and human females.

Animals↗
PubMed1983

Monoaminergic antagonists which block naloxone-induced release of luteinizing hormone bind selectively to hypothalamic opiate receptors.

The possibility that adrenergic receptor antagonists which prevent naloxone-induced release of luteinizing hormone (LH) in vivo exert their action by direct competition with naloxone for hypothalamic opiate receptors was investigated in vitro in immature female rats. First, 26-day-old rats were injected with prazosin, an alpha 1-adrenergic blocker, or yohimbine, an alpha 2-adrenergic blocker, before receiving naloxone (2.5 mg/kg body wt.). Both adrenergic antagonists prevented naloxone-provoked LH secretion in a dose-dependent manner with yohimbine exhibiting a slightly greater potency. In a separate experiment hypothalami from 26-day-old rats were removed, membrane pellets prepared and incubated with [3H]naloxone in the presence of increasing concentrations of naloxone or various monoamine-active substances. Phentolamine, prazosin and yohimbine were the most effective competitors for naloxone binding sites while pronethalol, methysergide and metergoline were far less effective. These findings parallel the relative inhibitory potencies of these compounds in vivo for preventing naloxone-induced LH release as shown here and in a previous report. Clonidine and L-phenylephrine, both alpha-adrenergic agonists, also showed activity in the binding assay. Surprisingly, alpha-methyl-p-tyrosine and 5-hydroxytryptophan, substances which substitute for monoamine precursors early in the biosynthetic pathway, also displaced [3H]naloxone from hypothalamic receptors. These results offer a mechanism for the modulating effects of monoamine-active drugs on opiate antagonist-induced LH release and may have significance for inhibition of LH secretion by endogenous opiates.

Animals↗