Biomedical subjects

M H Samuels

Publications and source records attributed to M H Samuels.

12 recordsLinked to original sources

PubMed1992

Cocaine impairs gonadotropin secretion in oophorectomized monkeys.

OBJECTIVE: Our objective was to determine whether cocaine alters gonadotropin secretion in oophorectomized monkeys. STUDY DESIGN: Oophorectomized monkeys with elevated gonadotropin levels were chronically cannulated to allow blood sampling every 15 minutes. Monkeys received either saline solution or 2 or 4 mg/kg cocaine hydrochloride as an intravenous bolus. Other oophorectomized monkeys were pretreated with either saline solution or 4 mg/kg cocaine 2 hours before bolus gonadotropin-releasing hormone administration, and plasma luteinizing hormone and follicle-stimulating hormone levels were measured every 15 minutes for 3 hours. Monkeys were also given either saline solution or 4 mg/kg of cocaine with gonadotropin-releasing hormone simultaneously, and plasma gonadotropin levels were measured every 15 minutes for 3 hours. Serum luteinizing hormone and follicle-stimulating hormone levels were measured by radioimmunoassay. RESULTS: Both doses of cocaine resulted in a significant decrease in luteinizing hormone levels compared with controls. Follicle-stimulating hormone levels were significantly decreased only with the 4 mg/kg dose of cocaine. There was no difference in luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the cocaine-treated monkeys compared with saline solution-treated monkeys by using repeated-measures analysis of variance. CONCLUSION: These findings demonstrate that acute cocaine administration to oophorectomized primates inhibits basal luteinizing hormone-follicle-stimulating hormone secretion but not gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone release. In the absence of an effect on gonadotropin-releasing hormone-stimulated gonadotropin release, we conclude that the impaired luteinizing hormone-follicle-stimulating hormone secretion after cocaine administration is due in part to a direct effect of cocaine on gonadotropin-releasing hormone neurons or on hypothalamic neurotransmitter modulation of gonadotropin-releasing hormone release.

Analysis of Variance↗

PubMed1992

Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion.

The hypothalamic factors dopamine (DA) and somatostatin (SRIH) inhibit pituitary glycoprotein secretion, but little is known regarding the effects of these factors on glycoprotein pulses. To address this question, 12 healthy volunteers underwent frequent blood sampling over 12 h at baseline and during 12-h infusions of DA and/or SRIH. TSH, LH, FSH, and alpha-subunit (alpha) levels were measured in all samples, and hormone pulses were located by Cluster analysis. Both DA and SRIH suppressed TSH pulse amplitude by 70%, while SRIH decreased TSH pulse frequency as well. Both infusions decreased LH pulse amplitude by 30-35%, but had no effect on pulse frequency. In contrast, neither infusion significantly altered FSH pulse parameters, although mean FSH levels declined 15%. DA had no effect on pulsatile alpha secretion, while SRIH decreased alpha pulse frequency. Serum thyroid hormone levels declined during both infusions, but there were no major changes in serum sex steroid levels. Thus, the hypothalamic inhibitory factors DA and SRIH had divergent effects on glycoprotein hormone pulses. The major effects on pulse amplitude, rather than frequency, imply that these factors do not play major roles in the generation of glycoprotein pulses, although SRIH may directly affect the TSH and alpha pulse generators.

Adolescent↗

PubMed1992

Central hypothyroidism.

Central hypothyroidism is an uncommon condition characterized by insufficient thyroid gland stimulation by TSH, owing to hypothalamic and/or pituitary dysfunction. It is rarely isolated but more often occurs in conjunction with deficiencies of other pituitary hormones, as well as with neurologic symptoms and signs owing to hypothalamic/pituitary lesions. The diagnosis rests on documentation of clinical and biochemical hypothyroidism with an inappropriately low or nonelevated serum TSH level. Recent studies suggest that the temporal pattern of TSH secretion, as well as TSH structure, is altered in central hypothyroidism, providing a mechanism for the induction of the hypothyroid state in this condition.

Animals↗

PubMed1991

Pulsatile glycoprotein hormone secretion in glycoprotein-producing pituitary tumors.

To study patterns of hormone production and secretion in glycoprotein-producing pituitary tumors, 12 patients with such tumors underwent the following studies. Preoperatively, all patients had serum TSH, LH, FSH, and alpha-subunit levels measured every 15 min for 24 h. Hormone pulses were located by cluster analysis, and pulse parameters were compared to those in healthy young men, healthy young women, healthy postmenopausal women, and subjects with primary hypothyroidism. After surgery, immunocytochemistry for the four glycoproteins was performed on all tumors, and Northern blot analysis was performed in six tumors with probes for the four subunits. By immunocytochemistry, 42% of the tumors were positive for TSH beta, 83% for LH beta, 75% for FSH beta, and 92% for alpha-subunit. Preoperative serum hormone levels varied widely between patients and were not well correlated with the intensity of immunocytochemical staining. Northern blot analysis did not appear to be as sensitive as immunocytochemistry for detection of the glycoproteins. All patients had pulsatile glycoprotein secretion, with pulses of normal frequency but varied amplitude. These results suggest that in patients with glycoprotein tumors, hormone pulses may be an integral part of autonomous secretion, or that hypothalamic control is involved in glycoprotein secretion and, perhaps, in the pathogenesis of these tumors.

Adenoma↗

PubMed1991

Pulsatile prolactin secretion in hyperprolactinemia due to presumed pituitary stalk interruption.

PRL, like other anterior pituitary hormones, is normally secreted in a pulsatile fashion. However, it is not known whether such pulses depend on dopamine and/or other hypothalamic factors. This question can be addressed by investigating patients with large pituitary mass lesions, since such patients often have hyperprolactinemia due to disruption of normal hypothalamic input to the pituitary gland. Six such patients (5 with non-PRL-secreting tumors and 1 with a craniopharyngioma) and 11 healthy control subjects had PRL levels measured every 15 min over 24 h. PRL pulses were located by cluster analysis. All patients had PRL pulses of normal frequency, but increased amplitude. Circadian variation in PRL pulse amplitude, present in healthy women, was abolished in tumor patients. These results imply that normal pituitary levels of dopamine do not control the generation of PRL pulses. Instead, PRL pulses may arise from the pituitary gland, with pulse amplitude and circadian rhythm modulation by dopamine and other hypothalamic factors. Alternatively, the mild hyperprolactinemia associated with large hypothalamic-pituitary tumors may represent partial impairment of dopamine secretion, with sufficient pituitary dopamine levels to maintain normal PRL pulse frequency.

Circadian Rhythm↗

PubMed1991

The role of endogenous opiates in athletic amenorrhea.

We hypothesized that menstrual disturbances in female athletes arise from opioid-induced abnormalities in gonadotropin and/or prolactin (PRL) secretion. To investigate this hypothesis, we measured luteinizing hormone, follicle-stimulating hormone, and PRL levels in eumenorrheic and amenorrheic athletes during thyrotropin-releasing hormone and gonadotropin-releasing hormone tests at baseline, after naloxone infusions, after exercise to exhaustion, and after similar exercise during naloxone infusions. Contrary to our hypothesis, amenorrheic runners did not have significant alterations in basal, postexercise, or stimulated hormone levels compared with eumenorrheic runners. In addition, opioid blockade by naloxone did not enhance gonadotropin release by amenorrheic athletes.

Adult↗

PubMed1990

Patterns of pulsatile pituitary glycoprotein secretion in central hypothyroidism and hypogonadism.

Five patients with central hypothyroidism and hypogonadism due to mass or infiltrative lesions of the pituitary and hypothalamus were studied to determine pulsatile pituitary glycoprotein secretion patterns. Blood samples were obtained every 15 min over 24 h, and TSH, LH and FSH were measured by immunoradiometric assays. Hormone pulses were located by cluster analysis, and pulse patterns were compared to those in normal subjects. Three patients had unmeasurable LH levels, while two had a normal number of low amplitude pulses. In contrast, all patients had normal FSH pulse frequency, and only one had low pulse amplitude. Three patients had normal 24-h TSH pulse frequency and amplitude, while two had slightly decreased pulse parameters. However, all failed to show normal nocturnal increases in TSH pulse amplitude. Thus, anatomical hypothalamic-pituitary lesions disrupt pulsatile glycoprotein secretion in a discordant fashion. LH is most severely affected, with abnormal pulse patterns similar to those in idiopathic central hypogonadism. FSH and TSH pulses are relatively preserved, but loss of the usual nocturnal increase in TSH pulse amplitude is sufficient to cause clinical hypothyroidism. Whether these defects reflect intrinsic pituitary disease or impaired hypothalamic releasing factor function remains to be determined.

Adolescent↗

PubMed1990

Pathophysiology of pulsatile and copulsatile release of thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and alpha-subunit.

Under physiological conditions, TSH, LH, FSH, and alpha-subunit are released in discrete pulses. To further characterize their neuroregulation and to investigate possible copulsatile secretion of these glycoprotein hormones, we studied the 24-h pulse profiles of all four hormones in each of four subject groups: young men, young women, postmenopausal women, and subjects with untreated primary hypothyroidism. Gonadotropin pulse properties in euthyroid men and women were similar to those previously reported, and hypothyroid subjects had normal gonadotropin pulse patterns. TSH release was pulsatile in all groups; hypothyroid subjects had increased pulse amplitude, but loss of the usual nocturnal increases in pulse amplitude. alpha-Subunit concentrations were pulsatile in all groups, with minimal circadian variation; postmenopausal and hypothyroid subjects had increased alpha-subunit pulse amplitude. We then tested pulse concordance among the four simultaneous hormone series. alpha-Subunit and the gonadotropins were significantly coreleased (triple coincidence), suggesting that all three hormones are closely linked to processes that regulate GnRH secretion. alpha-Subunit bursts were also significantly coincident with those of TSH in men, postmenopausal women, and hypothyroid subjects. Interestingly, TSH pulses were significantly concordant with those of LH and FSH, and all four hormones were significantly concordant in men, postmenopausal women, and hypothyroid subjects. In conclusion, the present findings imply that an underlying unified signal coordinates pulsatile hormone secretion from both gonadotrophs and thyrotrophs.

Adult↗

PubMed1990

Ectopic pituitary adenoma of the third ventricle. Case report.

Ectopic pituitary adenomas without associated intrasellar adenomas are rare and are usually located in the sphenoid sinus. Most have been reported without modern radiological, endocrinological, or electron microscopic (EM) documentation. The case of a 47-year-old man with a third ventricular, ectopic, clinically nonsecretory pituitary adenoma, which was shown to be a gonadotrophic adenoma by immunohistochemical and EM study, is reported. Neurological examination, extensive neurodiagnostic imaging, surgical anatomical observation, and endocrinological evaluation showed no evidence of neoplasia outside the third ventricle.

Adenoma↗

PubMed1989

The effect of altered thyroid status on pituitary hormone messenger ribonucleic acid concentrations in the rat.

To study the effects of altered thyroid status on pretranslational control of pituitary hormones, adult male rats were given propylthiouracil for 6 weeks and underwent the following studies. 1) Rats were injected with T3 at 10 micrograms/100 g BW daily for 10 days. 2) Rats were given T3 injections at 0, 0.01, 0.1, 1.0, or 10 micrograms/100 g BW for 10 days. 3) Rats were killed 0, 1, 6, or 24 h after a single injection of T3 at 10 micrograms/100 g BW or after 5 or 10 days of daily T3 injections. Pituitary mRNA concentrations of TSH beta, alpha-subunit, PRL, GH, POMC, FSH beta, and LH beta were determined for individual animals. Marked increases in TSH beta and alpha-subunit mRNAs occurred after PTU treatment, and these changes were reversed by 1.0 microgram/100 g BW T3 and within 24 h of a single T3 injection of 10 micrograms/100 g BW. Further increases in the dose or time course of T3 administration led to a relatively greater suppression of TSH beta mRNA levels than alpha-subunit mRNA levels. In contrast, GH and PRL mRNA levels were low in hypothyroid animals, and both rose toward control levels with 0.1 microgram/100 g BW T3 and by 24 h after a single T3 dose. Induction of hyperthyroidism did not further increase GH mRNA levels above control, but increased PRL mRNA levels 2-fold over control. No changes were seen in FSH beta, LH beta, or POMC mRNA levels with any treatment. Thus, studies of altered thyroid status in the rat reveal dose-response and time-course variability in the pretranslational control of TSH beta, alpha-subunit, GH, and PRL by thyroid hormone.

Animals↗

PubMed1989

Clinical and molecular studies of a thyrotropin-secreting pituitary adenoma.

A 40-year-old woman, who had previously received radioactive iodine for hyperthyroidism, presumably due to Graves' disease, subsequently was found to have inappropriately elevated serum TSH and alpha-subunit levels and a pituitary adenoma. Detailed clinical studies revealed marked serum TSH elevations (approximately 100 mU/L) with no circadian variation, but with 7 pulses/24 h. Serum alpha-subunit levels averaged 2.5 micrograms/L, with 13 pulses/24 h. Neither serum TSH nor alpha-subunit responded to TRH stimulation, nor did serum TSH change during dopamine infusion, but alpha-subunit levels did decline slightly. In contrast, during somatostatin infusion, serum TSH declined to 30% of baseline levels, while alpha-subunit levels did not change. Pituitary adenoma tissue obtained at the time of transsphenoidal surgery immunostained weakly with anti-TSH beta serum and strongly with anti-alpha-subunit serum. Northern blot analysis of RNA isolated from the tumor revealed TSH beta and alpha-subunit mRNA levels of normal length, while primer extension analysis showed a major initiation site for the TSH beta gene that appeared to be identical in the tumor and normal pituitary tissue. A second minor upstream start site was detected in the tumor, but it represented less than 1% of transcription compared to the major downstream start site. We conclude that the tumor secreted TSH and alpha-subunit in an abnormal and discordant fashion, but that the TSH gene initiation site appeared to be normal and, therefore, did not explain the observed secretory abnormalities.

Adenoma↗

PubMed1989

Massive insulin overdose: detailed studies of free insulin levels and glucose requirements.

The course of a diabetic patient who self-administered 2500 U of NPH insulin subcutaneously was examined in detail. Despite resumption of oral intake on day 3, she required iv glucose for 6 days, during which time serum free insulin levels remained elevated. Glucose requirements closely matched those calculated from published euglycemic clamp data on maximal glucose disposal rates during insulin infusion. We postulate that her prolonged course was due to delayed absorption of the subcutaneous insulin. This is the first case of massive insulin overdose studied in such detail, and the results may facilitate management of future cases.

Adult↗