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Biomedical subjects

W J Bremner

Publications and source records attributed to W J Bremner.

At least 145 records · Page 8Linked to original sources

Prolonged intravenous infusions of LH-releasing hormone into normal men.

Five normal men received constant intravenous infusions of luteinizing hormone-releasing hormone (LH-RH), 0.2 mug/min, for 14-19 hours. Serum levels ofluteizining hormone (LH) revealed a biphasic pattern of increase, reaching maximal values by 4 hours after the infusions began, then remained near that level until the infusions ceased. Serum follicle stimulating hormone (FSH) levels rose gradually to maximal values by 6-13 hours and maintained this level until the end of the infusions. Testosterone (T) levels revealed gradual increases throughout the infusions. These results confirm an increase in serum T levels with prolonged endogenous gonadotrophin stimulation. This is in contrast to the inability of several previous studies to demonstrate an increase in T levels following the relatively short gonadotrophin elevation produced by single-shot LH-RH administration. The T increases produced, however, were quantitatively much less than those reported during prolonged LH-RH infusions in rams, suggesting that the human testis is less responsive to endogenous gonadotrophin stimulation than is that of the ram. In addition, prolonged LH-RH stimulation did not cause pituitary refractoriness in men as has been described in animals.

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Increases in serum concentrations of follicle-stimulating hormone (FSH) during thyrotrophin-releasing hormone (TRH) infusions in normal men.

Increases in serum FSH values to approximately 50% above basal concentrations were found during TRH infusions of 2.0 microgram/min into normal men (n = 10). These increases could not be explained by cross-reactivity of thyrotrophin (TSH) in the FSH assay. No significant change was found in serum concentrations of FSH during saline infusions (n = 4) nor in LH concentrations during either TRH or saline infusions. Many previous studies using single injections of TRH have failed to demonstrate changes in serum FSH concentrations. It is possible that prolonged infusions of TRH, as used in this study, are more likely to lead to non-specificity of the effects of this tripeptide on pituitary hormone secretion.

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Pituitary autonomy in hyperprolactinemic secondary amenorrhea: results of hypothalamic-pituitary testing.

Twenty-seven women with secondary amenorrhea of greater than six months duration were subjected to multiple testing of hypothalamo-pituitary function. They were divided into normo-prolactinemic (Group 1 mean serum prolactin (PRL) 9.8 ng/ml; range 6.8 to 13.0 ng/ml; n=9) and hyperprolactinemic (Group 2 mean 37.5 ng/ml; range 19.2 to 93.7 ng/ml; n=18) groups on the basis of 4 weekly baseline determinations. Group 2 had significantly (P less than .05) lower serum LH and urinary pregnanediol levels than did Group 1; there was no statistical difference between the groups in serum FSH, T4, T3 or urinary estrogen measurements. Two women in Group 2 were found to have a pituitary chromophobe adenoma. Group 2 women showed no significant rises in serum PRL following stimulation tests with thyrotropin releasing hormone (TRH, 200 microng iv) and metoclopramide (10 mg orally), which caused significant responses in Group 1. The TSH response to TRH was, however, preserved in Group 2, while it was subnormal in Group 1 subjects. Both groups showed similar FSH and LH responses to luteinizing hormone-releasing hormone (LHRH, 25 microng iv). No significant suppression of serum PRL was seen in Group 2 patients given L-Dopa (500 mg orally),, which produced a significant response (P less than 0.05) in Group 1 subjects, while all patient showed marked reduction in serum PRL values following 2-bromo-alpha-ergocryptine (CB-154, 2.5 mg orally). When compared with other Group 2 members, the 2 cases with proven pituitary adenomata gave similar responses to the stimulation-inhibition tests and were not clearly distinguished on this basis. We conclude: 1. The pattern of PRL responses to dynamic tests, although of pathophysiological interest an autonomous pituitary lesions in patients with hyperprolactinemic secondary amenorrhea. 2. Such dynamic tests, although a pathophysiological interest, provide no clinical information additional to that provided by the mean basal serum PRL value. 3. In clinical practice, such dynamic tests should be confined to patients with mean serum PRL levels at around the upper limit of the normal range.

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The association of D-group chromosomal translocations and defective spermatogenesis.

D-group chromosome translocations have been associated in isolated cases with infertility in males. In this study, we demonstrated the effect of a translocated D-group chromosome on spermatogenesis as it had segregated among three male members of one family. Although the father, who carried the translocation, was obviously fertile, the effects of the translocations on his sperm were noted in the morphologic examination. This study demonstrates the need for more careful evaluation of patients with chromosomal abnormalities for effects on spermatogenesis. Furthermore, it shows the possibility of autosomal chromosomal influences on testicular function.

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The effect of testicular x-irradiation on spermatogenesis in man. A comparison with the mouse.

Existing data concerning the effects of x-irradiation on spermatogenesis in man were analyzed and the results were compared to published data on the mouse. Testicular x-irradiation produced a transient, but substantial, suppression of sperm counts in man, with an ED50 near 11 rad. The length of time to recovery was proportional to the irradiation dose. The ED50 for suppression of type A spermatogonia following radiation exposure in man was similar (9.7 rad), although the response curves for spermatogonia and sperm count were matogonia in the mouse was parallel to that found in man, but with an ED 50 of 30.0 rad. These results suggest that, compared to the mouse, spermatogenesis in man is approximately 3.1 times more sensitive to ionizing irradiation.

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Stimulation of sperm production by human chorionic gonadotropin after prolonged gonadotropin suppression in normal men.

The precise hormonal milieu required for quantitatively normal spermatogenesis in man is unclear. The authors previously have shown that both supraphysiologic dosages of human chorionic gonadotropin (hCG) and physiologic dosages of human luteinizing hormone (hLH) can reinitiate sperm production in short-term (four months) gonadotropin-suppressed normal men who have prepubertal FSH levels. To determine whether normal FSH levels were necessary to stimulate sperm production after a prolonged period of gonadotropin and testicular suppression, the authors administered hCG to four normal men whose endogenous gonadotropin levels and sperm production were suppressed by prolonged exogenous testosterone (T) administration. After a 3-month control period, all subjects received 200 mg of T enanthate intramuscularly (im) each week to suppress LH and FSH for a total of 9 months and until successive sperm concentrations (performed twice monthly) revealed azoospermia or severe oligozoospermia (mean sperm concentration less than 3 X 10(6) spermatozoa/ml) for 6 months. Then, while continuing the same dosage of T enanthate, all four men simultaneously received 5000 IU of hCG im three times weekly for 6 months, replacing LH-like activity and leaving FSH activity suppressed. The effect on sperm production of the selective FSH deficiency produced by hCG plus T administration after the period of prolonged gonadotropin suppression was determined. Exogenous T administration resulted in severe suppression of sperm concentrations from 79 +/- 7 X 10(6) spermatozoa/ml (mean +/- SEM) during the control period to 0.8 +/- 0.5 X 10(6)/ml after 12 weeks of T treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men.

The circadian pattern in levels of serum total testosterone (T) in men becomes blunted with normal aging. However, because T not bound to sex hormone-binding globulin (non-SHBG-T) is felt to be a better representative of biologically available T than is total T, the possibility of a 24-h variation in non-SHBG-T in young men and the possibility that aging is associated with a blunting of that rhythm were investigated. Hourly blood samples were drawn on 10 normal young men (mean age 27.3 years) and 10 normal elderly men (mean age 70.7 years) over a 24-h period and the serum was assayed for total T, sex hormone-binding globulin (SHBG), and total protein; non-SHBG-T was calculated. SHBG was determined by radioimmunoassay as well as by a steroid-binding assay. Young men had a significantly higher (p less than 0.05) mean 24-h level of non-SHBG-T (1.91 +/- 0.62 nm/l) than did the elderly men (0.86 +/- 0.01 nM/l). Also, each young man showed a significant circadian rhythm in non-SHBG-T, with a group mean daily variation of 1.42 +/- 0.38 nM/l. In contrast, only 60% of the elderly men demonstrated a significant circadian rhythm in non-SHBG-T, and the group mean rhythm was blunted (maximum excursion 0.38 +/- 0.07 nM/l) compared with that of the young men. SHBG and total protein levels demonstrated similar 24-h variations in the two age groups. It was concluded that non-SHBG-T serum levels, similar to serum total T levels, demonstrate a circadian pattern in young men and this circadian rhythmicity becomes blunted with normal aging.

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