J. Mahlstedt and K. Joseph
H. K. Dürr, H. Gerdes, and K. Joseph
K. M. Knigge and S. A. Joseph
The concentration of TRF in cerebrospinal fluid (CSF) of the 3rd ventricle and content of TRF in median eminence of the rat was examined. CSF (0.3–0.5 μl per animal) was collected from the 3rd ventricle by a microcannula technique and pooled samples from 10–15 animals were examined for TRF using an in vitro pituitary assay method. TRF concentration in 3rd ventricle CSF of normal male rats was 18.5 ± 4.2 pg/μl; median eminence contained 115 ± 12 pg. Cold exposure (4°C) for 16–18 h and thyroxine treatment (2.5 μg/day) for 5 days markedly reduced TRF concentration in CSF and content in the median eminence. Treatment with the anti-thyroid drug methimazole (0.01 % in the drinking water) for 5 days did not notably affect TRF in CSF or median eminence.
K. Joseph, J. Mahlstedt, and Th. Kranz
T Joseph McKenna and Sean K Cunningham
In the present paper we shall discuss adrenal androgen production in the context of polycystic ovary syndrome (PCOS). It appears to be well established that adrenal androgen production is abnormal in at least some patients with PCOS. Here we will discuss the evidence for abnormalities in adrenal androgen production, explore the underlying mechanisms and address the questions: are disturbances in adrenal androgen production primary or secondary phenomena? and, is there a role for treatment directed towards correction of adrenal androgen abnormalities in the management of PCOS?
The whole area surrounding PCOS and related conditions has been bedeviled by a lack of standardization in the definitions used. For this reason we will begin by defining the terms to be used in this paper and suggest a classification that may help to ensure that the topics under examination in this paper are delineated clearly.
Polycystic ovary syndrome (PCOS)
Polycystic ovary syndrome
George Sichuk, Joseph G. Fortner, and Bela K. Der
Prolonged administration of norethynodrel with mestranol had a pronounced and selective influence on hormonal target tissues in middleaged male hamsters. Results were compatible with work in other species, which shows the primary site of action to be the pituitary-gonad axis. Markedly reduced gonadotrophin and androgen levels were indicated by atrophy of testes and accessory reproductive glands. The high dosage used also resulted in significant renal hypertrophy, but structural integrity was not conspicuously different from that of controls.
The test agents had no influence on the incidence or metastatic propensity of a wide variety of spontaneous tumours, including adenomatous polyps and adenocarcinoma of the intestine, adrenal cortical nodular hyperplasia or adenoma, islet cell adenoma, melanoma, or adenocareinoma of Cowper's gland. This result is in accord with our previous observations that spontaneous tumorigenesis in the hamster is largely independent of hormonal physiology but is influenced by hormones to the extent that tumorigenesis may require some degree of normal tissue or cell integrity.
H. Bongers, L. A. Hotze, R. Schmitz, and K. Joseph
Abstract. Fifty-four patients with diffuse non-toxic goitre were observed before and under therapy either with 125 μg LT4 (group A) or 75 μg LT4 + 15 μg LT3 (group B) in a prospective double blind study, using 1-, 3- and 6-months controls. Changes in goitre size have been estimated by ultrasonic scanning. Both treatment forms provided a significant reduction of goitre size, even after 1 month of therapy: a 20%-decrease in group A and 16% in group B. The 6-month reduction was about 30% in group A and 27% in group B. Between the 2 groups there were no differences in the reduction of volume. The suppression of the TSH-response to TRH was identical in both groups, too. In group A there was a predominant increase of the TT4-and FT4-serum levels, both reaching the hyperthyroid range. In group B there was a predominant increase of the TT3- and FT3-serum levels and a slight increase of the FT4-levels. The TT3- and FT3-serum levels also exceeded the upper normal range. As the blood samples were drawn about 2 h after medication, acute hormone resorption influenced these data. In the 3-month controls only there was a significant correlation between the reduction of the thyroid volume and the suppression of TSH-release. In the 6-month controls we found a weak correlation of the reduction of volume and the decrease of the pertechnetate uptake value. No correlation was found between the relative changes of FT3- and FT4-serum levels and the reduction of goitre size. There were no indications of possible side effects in group A or B during treatment. So this study showed the compared treatment forms to be equivalent in the therapy of diffuse non-toxic goitre, both yielding excellent results.
Sean K. Cunningham, Therese Loughlin, Marie Culliton, and T. Joseph McKenna
Abstract. Hirsutism in women is a manifestation of escessive androgen action. This my be due to excessive exposure, or to increased sensitivity, of peripheral tissues to androgens. The present study was undertaken to estimate the percentage of hirsute patients with hyperandrogenaemia and to examine the effect of correction of hyperandrogenaemia on the clinical presentation. Plasma testosterone, dihydrotestosterone, sex hormone-binding globulin (SHBG) and androstenedione were determined in 58 hirsute patients before and following 3 months therapy with dexamethasone, 0.5 mg nocte. Testosterone expressed as a function of SHBG (testosterone/SHBG) provides an index of the non-protein bound testosterone fraction. Plasma levels of androstenedione were significantly elevated in 28% of hirsute patients, testosterone in 31% and testosterone/SHBG was elevated in 52%. Five per cent of patients had an elevated androstenedione value together with a normal testosterone/SHBG value. A subgroup of 13 hirsute patients with oligomenorrhoea had significantly higher values for androstenedione and testosterone/SHBG than eumenorrhoeic hirsute patients, and plasma testosterone, androstenedione and testosterone/SHBG values were more frequently elevated. In hirsute patients dexamethasone therapy resulted in suppression of plasma testosterone and androstenedione values, a significant increase in plasma SHBG and a marked fall in testosterone/SHBG. Following treatment with dexamethasone hyperandrogenaemia was corrected in 64% of hirsute patients, a decrease in the rate of hair growth or a resumption of a normal menstrual pattern occurred in 70% and concordant hormonal and clinical changes occurred in 79% of patients. These observations indicate that the testosterone/SHBG ratio is a sensitive index of hyperandrogenaemia, the correction of which is associated with clinical improvement.
Tarek M Fiad, Sean K Cunningham, and T Joseph McKenna
Fiad TM, Cunningham SK, McKenna TJ. Role of progesterone deficiency in the development of luteinizing hormone and androgen abnormalities in polycystic ovary syndrome. Eur J Endocrinol 1996;135:335–9. ISSN 0804–4643
The aetiology of polycystic ovary syndrome (PCOS) is unknown. It is uniquely characterized by oligomenorrhoea or amenorrhoea associated with normal or high oestrogen levels. This prospective clinical study was designed to examine the possible role of the lack of cyclical exposure to progesterone in the development of gonadotrophin and androgen abnormalities in PCOS. Gonadotrophin, androgen and oestrogen levels were measured in 15 PCOS patients and 10 normal subjects untreated and following treatment with the progestogen medroxyprogesterone acetate (MPA). When compared to control subjects, PCOS patients had significantly higher luteinizing hormone (LH) pulse height, pulse amplitude, integrated LH levels, LH response to gonadotrophin-releasing hormone (GnRH) and LH/FSH ratio; LH pulse frequency was similar in the two groups. In addition, the testosterone/sex hormone binding globulin ratio (T/SHBG), androstenedione and oestrone concentrations in the plasma were significantly higher in PCOS than in control subjects. When PCOS patients were treated with MPA for 5 days, there were significant decreases (p < 0.02–0.001) to values no longer different from normal: from 8.7 ± 1.2 to 5.6 ± 0.8 IU/l for integrated LH levels (untreated and MPA-treated PCOS); from 31.2 ±3.5 to 12.9 ±1.5 IU/l for LH response to GnRH; from 2.4 ± 0.26 to 1.3 ± 0.2 for LH/FSH ratio; and from 10.4 ± 0.63 to 8.5 ± for androstenedione. Significant decreases (p < 0.05–0.005) to values that still remained significantly higher than in normal subjects occurred for: LH pulse height, 11.05 ± 1.3 to 6.88 ± 0.79 IU/l (untreated and MPA-treated PCOS); LH pulse amplitude, 2.8 ± 0.5 to 1.8 ± 0.2 IU/l; total testosterone, 2.5 ± 0.2 to 2.0± 0.2 nmol/l; T/SHBG ratio, 14.1 ± 1.7 to 11 ± 1.5; and oestrone, 265 ± 24 to 208 ± 29 pmol/l. These results are consistent with the concept that ovulation failure and progesterone deficiency play a facilitatory role in the development of the hypothalamic-pituitary abnormality giving rise to disordered LH secretion in PCOS.
TJ McKenna. Department of Investigative Endocrinology. St Vincent's Hospital, Elm Park. Dublin 4, Ireland