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ABSTRACT
The effect of oestradiol-17β on the hypothalamo-pituitary axis of intact adult male rats was studied. A single injection of oestradiol did not change the serum LH response to gonadotrophin-releasing hormone (GnRH) 48 h or 7 days after the injection, while administration of oestrogen over 66 days suppressed basal serum LH to <3·1 μg/l and did not enhance the LH response to GnRH at any time.
Treatment of ovariectomized rats with oestradiol capsules, however, enhanced the LH response to GnRH on days 3 and 14 of the treatment as compared with the control group (P<0·02 and P<0·05 respectively). Long-term treatment with oestradiol suppressed intrapituitary LH and FSH contents as well as pituitary GnRH receptors (P<0·0004, P<0·005 and P<0·001 respectively), whereas serum and intrapituitary prolactin levels were increased. To exclude the possible inhibitory effect of hyperprolactinaemia on LH responsiveness to GnRH, oestradiol-implanted rats were treated with bromocriptine. This prevented the rise in serum prolactin, but failed to enhance the LH response to GnRH.
Neither short- nor long-term treatment with oestradiol given under conditions shown to be effective in female animals stimulated the hypothalamo-pituitary-gonadotrophin axis in adult male rats.
J. Endocr. (1987) 114,95–101
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SUMMARY
Ovarian metabolism of C19-steroids and oestrogens has been assessed at ovarian wedge resection in 22 patients with polycystic ovaries. There were marked variations between different patients.
High concentrations of androstenedione were found in ovarian vein plasma in some patients, and always after stimulation with human pituitary follicle-stimulating hormone (HP-FSH) in vivo. Its contribution to the daily production of testosterone has been considered. No measurable amounts of testosterone or dehydroepiandrosterone were found. Oestradiol concentration was sometimes normal or above.
Large amounts of androstenedione were generally isolated from cyst fluid. Occasionally testosterone was found and also epitestosterone after FSH. That concentrations of oestrogens in cyst fluid are low was confirmed, but sometimes higher levels were found after FSH.
Slices of ovarian tissue generally converted progesterone or pregnenolone to androstenedione in high yield but conversion to oestrogen appeared to be low. However, the difficulty of making quantitative comparisons by this method, in the absence of knowledge of the sizes of the pools of endogenous steroids in the tissue, has been recognized.
No evidence was found in any of the 18 cases examined for a lack of 3β-hydroxysteroid dehydrogenase.
In vitro synthesis of epitestosterone by both normal and polycystic ovaries has been observed.
A coincidental granulosa cell tumour in one patient synthesized testosterone in high yield.
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Queen Elizabeth Hospital, Birmingham, B15 2TH, and *Department of Clinical Endocrinology, Women's Hospital, Birmingham, BU 4HL
(Received 19 January 1976)
Administration of the natural or synthetic decapeptide known as luteinizing hormone/follicle-stimulating hormone releasing hormone (LH-RH) causes prompt release of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The decapeptide has a short half-life of only a few minutes, so that its use as a therapeutic agent in the treatment of infertility is limited. Attempts have been made therefore to synthesize more potent and longer-acting analogues. Many of these have only weak activity in experimental animals, but some, notably those with modifications to structure at residues 5, 6 and 10, are more effective (Arimura, Vilchez-Martinez, Coy, Coy, Hirotsu & Schally, 1974; Kastin, Arimura, Gonzalez-Barcena, Coy, Clinton-Miller, Nishi, Lee, Duron-Huerta, Schalch & Schally, 1974a; Kastin, Schally, Gonzalez-Barcena, Coy, Clinton-Miller, Porias & Schalch, 1974b; Vilchez-Martinez, Coy, Arimura, Coy, Hirotsu & Schally, 1974; Zañartu,
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SUMMARY
The effect of alterations in catecholamine metabolism on arginine-induced insulin release was studied in the anaesthetized rat. Alpha-methyl-p-tyrosine, which inhibits catecholamine synthesis, guanethidine, which prevents catecholamine release, and reserpine, which depletes catecholamine stores, all enhanced the secretion of insulin and reduced the rise in blood glucose after the amino acid load. Adrenalectomy, with or without corticosterone replacement, had a similar effect. Adrenaline inhibited the insulin response to arginine. It was concluded that in the rat, adrenergic mechanisms modulate the insulin response to arginine.
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SUMMARY
Thirty-five male patients with hypogonadism (excluding those suffering from complete hypopituitarism) have been studied. A system of classification is outlined based on the following features: (1) the clinical picture; in particular, evidence for androgen deficiency, (2) the histology of the Leydig cells, (3) the function of the seminiferous tubules as assessed by histology and sperm counts in semen, and (4) the excretion of gonadotrophins. The patients have been classified into those with primary testicular failure and those with failure of pituitary gonadotrophin secretion; the former group includes the patients with Klinefelter's syndrome. Difficulties arose in deciding when gonadotrophin excretion was definitely subnormal because the values in the lower part of the normal range overlap some of those from patients who were obviously deficient in pituitary gonadotrophin.
Some patients showed evidence of hypothyroidism, probably related to testosterone deficiency.
The excretion of 17-oxosteroids is shown to be a poor guide to the assessment of androgen deficiency. This is partly due to the secretion of adrenal androgen, which may be greater than normal in some patients with Leydig-cell deficiency. Patients with primary Leydig-cell failure responded to stimulation by corticotrophin (ACTH) with a relatively greater increase in 17-oxosteroids than normal. Patients with deficiency of pituitary gonadotrophin responded to ACTH stimulation with a much smaller increase in 17-oxosteroid excretion than normal individuals. The evidence presented suggests that a mechanism exists for the integration of androgen production by both gonad and adrenal.
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SUMMARY
C19-steroids, testosterone and oestrogen production rates have been measured simultaneously by urinary isotope dilution in a group of 18 patients with polycystic ovaries and in two normal women.
The production of total C19-steroids remained high in seven patients under dexamethasone suppression, suggesting a major ovarian contribution. In eight it did not remain high, suggesting a major adrenal contribution.
The rate of testosterone production was usually normal under dexamethasone. The rate of oestrogen production was not subnormal and even occasionally raised.
Ovarian wedge resection produced a good clinical response in 75% of the observations, and C19-steroid production fell. The latter was not so evident if there was no clinical response. Testosterone production was usually reduced. Oestrogen production rate changed irregularly.
Administration of human pituitary follicle-stimulating hormone caused a concurrent increase in C19-steroids, testosterone and oestrogen production in four out of five patients.
The inadequacy of the urinary isotope dilution technique, in attempting to measure testosterone secretion and interconversion of testosterone and androstenedione in these patients, has been stressed and discussed.
Some correlations have been established with direct observations on ovarian steroid metabolism in certain patients reported elsewhere.
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SUMMARY
1. Various parameters of androgen metabolism have been studied in a group of 11 hypogonadal men. They included the rates of: 17-oxosteroid excretion, total production of C-19 steroids, secretion of testosterone and total production of testosterone (including testosterone converted peripherally from other steroids). The concentrations of testosterone and androstenedione were also measured in peripheral and testicular venous plasma. In addition the effects of stimulation and suppression of adrenocortical function and of testicular stimulation were studied.
2. The patients were divided into three groups according to clinical features, gonadotrophin excretion and testicular histology and an attempt was made to correlate these tests with the steroid studies.
3. Patients with poorly developed secondary sexual characteristics had a low testicular secretion of testosterone. There was also an indication that in these cases the adrenal gland contributed significantly to the plasma testosterone.
4. Methods involving estimations of androgens in blood are shown to be of more value than estimations in urine. In some instances anomalous results were obtained for the rates of secretion of testosterone. The possible significance of these anomalies is discussed.
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SUMMARY
A patient is described who showed evidence of 25 years' duration of intermittent hyperadrenocorticalism due to adrenocortical hyperplasia. The most pronounced clinical symptom was oedema formation, which was shown to be associated with phases of increased adrenocortical activity. Cortisol secretion rates, for example, ranged from 24 to 161 mg./24 hr. There was also potassium depletion.
The response to dexamethasone was repeatedly anomalous, there being a tenfold increase in excretion of urinary 17-hydroxycorticosteroids. Responses to metyrapone and pyrogen were absent but the response to insulin appeared excessive. There was no alteration by dexamethasone in vitro of synthesis of cortisol or corticosterone. Binding of plasma cortisol and corticosteroid-binding globulin were decreased.
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SUMMARY
The hormonal effects of tamoxifen (10 mg daily for 6 months) have been studied in nine men with oligospermia. Basal concentrations of serum LH (1·7 ± 0·1 (s.e.m.) i.u./l) increased to a maximum of 4·1 ± 1·3 i.u./l (P < 0·001) after 6 months, and FSH rose from 4·9 ± 1·0 to a maximum of 7·7 ± 1·3 i.u./l after 4 months of treatment (P < 0·01).
The response to luteinizing hormone releasing hormone (LH-RH) was studied at monthly intervals. Sums of increments of serum LH increased from 35 ± 4 to 92 ± 17 i.u./l at 4 months (P < 0·001) and of FSH from 14 ± 3·4 to 23 ± 3·5 i.u./l at 4 months (P < 0·01).
Basal serum androgens rose from 25 ± 2·7 to 38 ± 2·4 nmol/l after 4 months of treatment (P < 0·05), and serum oestradiol-17β increased from 185 ± 25 to 631 ± 90 pmol/l by 6 months (P < 0·001). No significant changes occurred in sperm counts.
Five normal men acted as controls: they were given tamoxifen for 1 week. No significant changes were observed in serum LH, FSH or release of these hormones following administration of LH-RH. Serum androgens and oestrogens however, increased significantly by day 4 of treatment (P < 0·05).
