bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progestational Activity of Natural and Synthetic Androgens
Authors: Jänne O. , Hemminki S. , Isomaa V. , Kokko E. , Torkkeli H. , Torkkeli T. , Vierikko P. 
Published: May 2008

Uteroglobin, a progesterone‐regulated secretory protein in rabbit uterus, was used as a marker protein for studies on progestational activity of various natural and synthetic androgens. All the androgens investigated were able to induce uteroglobin synthesis in rabbit uterus; some of the synthetic androgens were even better inducers than progesterone itself. Our results suggest that androgens elicit their regulatory action on uteroglobin synthesis by way of progestin receptor mechanism, since: (i) There was an intimate correlation between the in vitro binding affinity to progestin receptor and the in vivo potency of the androgens to induce uteroglobin synthesis; (ii) Androgens were able to translocate cytosol progestin receptors to uterine nuclei; (iii) Dose‐response curves for uteroglobin induction were parallel for androgens and progestins, and (iv) Flutamide, a non‐steroidal antiandrogen, did not abolish androgen‐induced synthesis of uteroglobin or androgen‐promoted nuclear translocation of cytosol progestin receptors.Both progesterone and androgens seem to control uteroglobin synthesis through mechanisms involving formation of new mRNA species, since in each case there was an increase in the uterine preuteroglobin‐mRNA activity, as evaluated by a cell‐free in vitro translation assay, which correlated with the amount of uteroglobin secreted into the uterine fluid. Some of the androgens studied (7α, 17α‐dimethyl‐19‐nortestosterone, 17α‐ethyl‐19‐nortestosterone and 11‐methylene‐17α‐methyl‐19‐nortestosterone) enhanced uteroglobin synthesis to the same or greater extent than progesterone. Interestingly, these steroids are also known to be very potent androgens. The progestational actions of androgens may be applicable to human tissues, too, since all the androgens investigated were bound by the human uterine progestin receptor in a fashion identical with the rabbit receptor.
Regulation of Leydig Cell Function by Prolactin, Growth Hormone and Luteinizing Hormone
Authors: Payne Anita H. , Zipf William B. 
Published: May 2008

The effects of prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) on testicular LH receptor concentration and on testosterone synthesis in response to LH (testicular responsiveness) was studied in mature intact and hypophysectomized rats. Hypophysectomy reduced LH receptor concentration by 80% and testicular responsiveness to LH by 70%, 7 days after surgery. Daily treatment with LH initiated immediately following surgery resulted in a further dose‐dependent decrease in LH receptors and a dose‐dependent increase in testicular responsiveness. Loss of LH receptors was not due to occupancy of the receptor by exogenous LH. PRL (150 μg/day) or GH (150 μg/day) partially prevented the loss of LH receptors in hypophysectomized saline‐treated rats. The effect of PRL plus GH on LH receptor concentration was additive. The combination of LH (5 μg/day), PRL and GH prevented any loss of LH receptors after hypophysectomy. A positive effect of LH on its receptor occurred in the presence of PRL. Treatment of hypophysectomized rats with 5 μg LH + 150 μg PRL enhanced the effect observed with PRL alone on maintenance of LH receptors. PRL, administered together with higher doses of LH (25 or 50 μg/day) prevented LH from exerting a negative effect on LH receptor concentration. Similar treatment with GH plus LH neither allowed a positive effect of LH nor prevented higher doses of LH from exerting a negative effect on LH receptor concentration. Loss in testicular LH receptors was also demonstrated in intact rats which received a single administration of LH. Administration of 150 μg PRL for 3 days partially prevented the LH‐induced loss in LH receptors, while treatment with 150 μg GH had no effect on LH‐induced loss of testicular LH receptors.Despite the ability of PRL to increase LH receptor concentration in hypophysectomized rats, PRL treatments did not enhance testicular responsiveness to LH. Only when LH was administered together with either PKL or G H was testicular responsiveness to LH maintained at intact control values. These data indicate that 1) maintenance of testicular LH receptor concentration in adult hypophysectomized rats is dependent on the combined effects of PKL, GH and LH; 2) PRL not only prevents LH from exerting a negative effect, but allows LH to have a positive effect in the hypophysectomized rat on the testicular LH receptor; 3) PRL and GH appear to act at different sites and by different mechanisms; and 4) hormonal regulation of L H receptor concentration appears to be distinct from hormonal regulation of testicular responsiveness to LH.
A New Binding Model: Gonadotropin Induced Inhibition of Testicular Functions via Receptor or Ethanol Soluble Factor Dissociation
Authors: Bhalla Vinod K. 
Published: May 2008

The validity of the rapid equilibrium model as applied to the binding reaction between hLH/hCG and particulate receptors of rat testis is seriously challenged. The reaction is irreversible in nature and does not provide a reliable estimation of hormone affinity at different receptor concentrations. The effect of reaction volume alone in the binding reaction yields kd and Bmax values which show a definitive trend of receptor dissociation at higher reaction volumes. Buffer‐induced receptor loss from its particulate form is correlated with the recovery of ethanol‐soluble factors (J. biol. Chem. 251, 4947, 1976) in homogenate supernatants. In addition, time and buffer dependent loss of receptors from intact testes is also correlated with the appearance of ethanol‐soluble factors in the eluates by a perifusion technique.Pretreatment of the testicular homogenate in vitro with 5 % ethanol reduces the number of receptor sites, an observation which is confirmed by in vivo administration of 20 % ethanol solution into adult male rats. Ethanol administration causes a dramatic reduction in the concentrations of LH specific receptor sites in the testis.Taken together, the data refute the equilibrium binding model and support a new model which takes into consideration the basal level of receptor dissociation and predicts that increasing unlabelled hormone concentrations in the binding assays reduce the receptor population in the target tissue in a dose dependent manner. The significance of this model which adequately represents the data of many investigators including our own, is described.
Effects of Oestrogens and FSH on LH Stimulation of Steroid Production by Testis Leydig Cells from Immature Rats
Authors: van Beurden Wilma M. O. , Roodnat Bep , van der Molen Henk J. 
Published: May 2008

Hypophysectomy of immature male rats results after 5 days in a decreased production of testosterone by isolated testis Leydig cells in response to LH. The LH responsiveness of the Leydig cells can be partly restored by treatment of the hypophysectomized rats with FSH. In continuation of previous reports on this subject (Steroids 28 (1976) 847; and 30 (1978) the following conclusions were derived from the results in the present paper:1. After hypophysectomy of immature male rats the production of testosterone (T) as well as of 5‐pregnenolone (Δ5P) by isolated Leydig cells in response to LH is reduced.2. Daily administration of FSH after hypophysectomy restores the Δ5P production in response to LH almost completely, but has a much smaller effect on the restoration of T production.3. Administration of oestradiol benzoate (E2B) together with FSH has no effect on the restoration of LH‐stimulated Δ5P production, but causes a reduction of T production, when compared with Leydig cells from animals treated with FSH only.4. Treatment of intact immature rats with E2B results in a decreased production of T and an increased production of Δ5P in isolated Leydig cells.5. From experiments with labelled pregnenolone it appears that E2B and diethylstilboestrol (DES) inhibit the 17α‐hydroxylase activity of Leydig cells from intact as well as from hypophysectomized rats. This results in a reduced conversion of pregnenolone to C1:)‐steroids and in increased production of 3α‐hydroxy‐5α‐pregnan‐20‐one from δ5P.6. The observed effects of FSH and E, were similar within a dose range of 100–10000 ng LH per 106 Leydig cells.
Structural Requirements for Steroid Binding to Androgen Binding Proteins
Authors: Tindall D. J. , Cunningham G. R. , Means A. R. 
Published: May 2008

The physicochemical properties of androgen binding protein (ABP) and sex steroid binding globulin (SBG) are virtually indistinguishable, whereas both of these proteins are remarkably different from the androgen cytoplasmic receptor (CR). Certain compounds, such as cyproterone acetate and BOMT, inhibited binding of labelled androgen to CR but did not inhibit binding to ABP. These data suggested that a fundamental difference exists between the binding sites of ABP and CR. We have therefore examined the steroid specificity of binding to a large number of steroidal compounds in order to characterize the binding sites of these binding proteins and to determine their binding specificities. Binding to partially purified ABP and SBG was assayed by a modification of the steady‐state PAGE technique described by Ritzen et al. (1974) by dissolving competitive inhibitors along with 0.2 nM 3H‐DHT in the gel solution. Binding of CR was assayed by the ammonium sulfate precipitation assay described by Verhoeven et al. (1975).A group of steroids was found which had high affinity for CR but low affinity for ABP. The structures of those steroids revealed that alterations at position 11 resulted in the greatest changes in binding affinity for ABP without changing significantly the binding affinity for CR. Whereas removal of the 19‐methyl group reduced binding for ABP, CR was not affected.A second group of steroids had high affinity for ABP but low affinity for CR. The structures of these compounds demonstrate that modifications at positions C‐2 and C‐17 resulted in the greatest changes in affinity for CR without significantly changing the binding affinity for ABP. The 3‐keto and 17α‐hydroxy moieties appear to be essential for CR binding, whereas both of these positions can be modified and still maintain ABP ***
Methods for Evaluation of Antifertility Agents in the Male
Authors: Hammerstein J. , Brotherton Janet 
Published: May 2008

The attainment and maintenance of azoospermia is first discussed as a parameter of the evaluation of antifertility agents in the male. Dangers lie in the possible non‐return of spermatogenesis and in practice the agents currently under test do not produce complete azoospermia. The relationships of fertility to sperm count, sperm motility and the proportion of spermatozoa with normal morphology is reviewed and found to be unreliable parameters in this respect. Their relative importance is believed to increase in the order indicated. Acid phosphatase, fructose and glycerophosphorylcholine should be measured as minimal parameters of the function of the prostate gland, the seminal vesicles and the epididymis respectively. All these parameters show great day‐to‐day variations requiring multiple estimations over long periods to indicate any real changes.Sperm migration into midcycle cervical mucus in vitro (Kremer test) is recommended as a much more reliable indicator of potential fertility of a semen specimen on the basis of results presented for a trial with cyproterone acetate at 10 mg/day orally. During the treatment phase the sperm migration index in this test was consistently below the accepted level of fertility. Such spermatozoa also failed to migrate into the uterus of tubal‐ligated women whose husbands were taking the drug as indicated by uterine sperm recovery tests using a washing procedure. Finally, progress that has been made in the development of an in vitro fertilisation test for human spermatozoa is discussed. Possibilities are the use of dead human ovarian oocytes or of the zona‐free oocytes of laboratory animals.
Gonadotropin Suppression in Normal Males and Males with 1° Hypogonadism: Evaluation of Four Androgens
Authors: Cunningham G. R. , Silverman V. , Kohler P. O. 
Published: May 2008

Serum concentrations of FSH and LH have been evaluated during treatment with four commonly prescribed androgens. In the first study, five adult males with primary gonadal failure were treated for four weeks with each of four regimens: 17α‐methyl testosterone [MT] (40 mg/day or 50 mg/day), fluoxymesterone [F] (50 mg/day), and testosterone cypionate [TC] (200 mg). LH was not suppressed by either dose of MT but was suppressed by F (P < 0.02). Both FSH and LH were suppressed for up to 3 weeks (P < 0.05) after a single injection of TC. In the second study, testosterone enanthate [TE] was evaluated as a contraceptive in 20 normal men. After two weeks (200 mg/week), the concentration of testosterone increased from 661 ± 29 ng/dl to approximately 1050 ng dl (P < 0.001) and serum gonadotropins had fallen to very low or undetectable levels. After 12 weeks of this regimen, 11 men had ≤ 1 million sperm/ml of semen, but 3 had ≥ 10 million sperm/ml. When 200 mg of TE was given every 3 weeks, serum levels of FSH and LH normalized and sperm density increased.These studies indicate that exogenous androgens can be used to suppress gonadotropins and spermatogenesis; however, each of these four available androgens has limitations. A more potent, longer acting androgen with low toxicity is needed if this approach to the development of a male contraceptive is to be pursued.
Testicular Steroid Metabolism In Vitro and Spermatogenesis in a Male with an XYY‐Karyotype
Authors: Kjessler B. , Berg A. Å:son 
Published: May 2008

Males with a 47, XYY‐chromosomal constitution have been reported to generally suffer from an impaired gametogenesis, and the reason for this spermatogenetic failure is unknown.The concentration of gonadotrophic hormones and testosterone in the peripheral circulation of XYY‐males have not been found to differ significantly from normal control subjects, but so far there is a lack of information on the intratesticular steroid conversion patterns in such individuals.We have repeately analysed the metabolism of [3H] progesterone in vitro in incubated testicular biopsy specimens derived from an XYY‐male before and after gonadotrophic substitution therapy. In addition hormone levels in peripheral blood samples, gametic output and testicular histopathology were investigated.The present patient was a 34‐year‐old healthy, but infertile male with a 47.XYY‐karyotype. His gonads were reduced in volume (6–8 ml) and displayed a heterogenous morphological picture. The appearance of the tubules varied from normal to complete destitution of germinal cells. The Leydig cell apparatus appeared normal. Serum levels of FSH, ICSH (LH) and testosterone were repeatedly within normal limits. The seminal fluid contained less than 10 mill. sperm per ml.Incubated testicular biopsy specimens metabolized [3H] progesterone in vitro mainly to 20α‐dihydroprogesterone (20α‐DH‐P) and to a less extent to 17α‐hydroxyprogesterone (17α‐OH‐P). Thus, the ratio 20α‐DH‐P:17α‐OH‐P was found to be remarkably high, i.e. an immature pattern often observed in prepubertal testicular tissue (Berg et al. 1976). By exogenous administration of gonadotrophic hormones to the present patient the steroid metabolic pattern in vitro changed in favour of an increased production of 17α‐OH‐P, concomitantly with an observed rise in gametic output.
Studies on the Relationship Between Sperm Count and Steroid Levels in the Spermatic and Cubital Veins of Patients With Varicocele
Authors: de la Torre B. , Norén S. , Hedman M. , Diczfalusy E. 
Published: May 2008

The levels of 10 unconjugated and 5 sulphurylated neutral steroids were assayed following chromatographic purification by radioimmunoassay procedures in the blood plasma obtained simultaneously from the left spermatic vein and cubital vein of 13 patients with varicocele.The levels of all unconjugated steroids as well as those of sulphurylated pregnenolone and sulphurylated testosterone were significantly higher in the spermatic vein than in the cubital vein.The ratios of the levels in spermatic to peripheral blood were highest in the case of testosterone (68.1), 17‐hydroxyprogesterone (61.2) and androstenedione (14.7) and lowest in the case of cortisol (1.3), suggesting that the former three steroids represent major secretory products of the human testis.The levels of pregnenolone, 17‐hydroxypregnenolone and dehydroepiandrosterone in spermatic vein were significantly correlated to those in the cubital vein.The peripheral plasma levels of 17‐hydroxypregnenolone, dehydroepiandrosterone, 17‐hydroxyprogesterone and testosterone in varicocele patients exhibiting severe oligospermia were significantly lower than those found in their normospermic counterparts. The levels of progesterone in the spermatic vein blood were also significantly lower in the oligospermic than in the normospermic group.The results indicate that in man, there is a significant relationship between the spermatogenic process and the profile of steroids secreted by the testes.
A Longitudinal Study of Pubertal Development in Boars Investigation of the Relationships Between Gonadal and Epididymal Development and Plasma Luteinizing Hormone and Testosterone Profiles
Authors: FlorCruz S. V. , Lapwood K. R. 
Published: May 2008

A longitudinal study was undertaken to evaluate the course of gonadal and epididymal development, and the concurrent endocrine changes during the period of sexual maturation, in Large White x Landrace boars.Twenty‐four animals were castrated sequentially at ages ranging from 43 to 241 days. Increases in testicular weights were more highly correlated with body weight (r = 0.953, P<0.001) and age (r = 0.919, P<0.001) than were similar increases in epilidymal weights (r = 0.558 and 0.593, P < 0.01, respectively). The age at onset of spermatogenesis varied between boars in the range 90 to 127 days. First observations of spermatozoa in seminiferous and epididymal tubules were made at 127 and 146 days of age respectively. Epididymal spermatozoal reserves per epididymis (ESR) were zero prior to 146 days of age; from that age mean ESR values increased progressively from 5.54 times 109 to 130 times 109 at 241 days of age.Longitudinal profiles of luteinizing hormone (LH) and testosterone secretion were investigated by assaying plasma samples collected at fortnightly intervals from each of ten boars aged 42 to 236 days. Until 82 days of age mean LH levels were low (0.20–1.25 ng/ml), then rose to a peak of 2.19 ng/ml at 110 days. Later LH levels declined gradually and after 166 days fluctuated between 0.5 and 1.0 ng/ml. Mean testosterone levels also were low in the prepubertal period (0.10–0.27 ng/ml), then between 110 and 138 days increased from 0.60 to 8.00 ng/ml. Subsequently testosterone concentrations fell slowly, then except for an isolated peak of 7.73 ng/ml at 194 days, fluctuated between 1.40 and 3.80 ng/ml. Castration ***
Testicular Development in the Unilaterally Cryptorchid Rat
Authors: Bergh A. , Helander H. F. 
Published: May 2008

By cutting the distal part of gubernaculum testis in newborn rats cryptorchism was produced. This new method to obtain cryptorchid animals has the advange of preventing testicular descent before it normally takes place, thus mimicking congenital cryptorchism. Unilaterally cryptorchid rats were examined at 20, 30 and 100 days of age. Morphometric methods were used to compare the structure of the abdominal and the scrotal testicles during development. In the abdominal testicles some tubular cells were damaged already at 20 days of age, i. e. when the temperature difference between the testicles probably is quite small.In the abdominal testicles the pathological changes of the tubules precede those of the interstitium. The descended testicles of unilaterally cryptorchid rats were identical to testicles of normal control rats, and all the operated rats were fertile at adult age.
Influence of Antiandrogens on Sertoli Cell Function and Intratesticular Androgen Transport
Authors: Schenck B. , Neumann F. 
Published: May 2008

The effect of cyproterone acetate (CA) on spermatogenesis and especially on Sertoli cell function was investigated. Male rats were treated with daily doses of cyproterone acetate ranging from 0.625 to 30 mg/day sc for six weeks.The highest dose of cyproterone acetate inhibits spermatogenesis and reduces testicular weights as well as ABP content and concentration in the capita epididymis of treated rats, whereas serum FSH, LH and testosterone concentrations remain unaffected by cyproterone acetate treatment. These findings demonstrate that cyproterone acetate acts directly upon the testis and inhibits Sertoli cell function, as reflected by decreased ABP production.The binding studies revealed that cyproterone acetate does not compete with androgens for binding to ABP and, therefore, has no other effect on androgen transport in the testis than inhibition of ABP production. The nonsteroidal antiandrogen, flutamide, behaves like cyproterone acetate in respect of its binding to ABP, whereas SKF 7690 competes with DHT.
Amniotic Fluid Androgens and their Relationship to Foetal Sex
Authors: Lox Charles D. 
Published: May 2008

Levels of testosterone (T), dihydrotestosterone (DHT), and androstenedione (A) in amniotic fluid taken before twenty weeks of gestation were measured by radioimmunoassay in 37 patients with female foetuses and 45 patients with male foetuses.Androstenedione levels were not significantly influenced by foetal sex. While DHT levels were undetectable for both sexes, the levels of T were significantly higher in the amniotic fluid surrounding the male foetus when compared to that surrounding the female foetus (X̄= 184 pg/ml for males and 58 pg/ml for females).Testosterone concentration in the amniotic fluid still appears to be the best hormonal indicator of foetal sex in utero.
Cytological Studies of Prostatic Fluids from Men With and Without Abnormal Palpatory Findings of the Prostate II. Clinical Application
Authors: Eliasson R. , Johannisson E. 
Published: May 2008

Exfoliative cytology of the fluid from human prostate and/or seminal vesicles has been used for diagnosis and follow‐up of inflammatory conditions in these glands. Forty‐one men with a barren union and obvious cytological and/or palpatory signs of inflammation of the prostate or seminal vesicles were included and three men had cytological evidence of slight inflammation. Thirty‐four men had an abundance of inflammatory cells in the expressed fluid and severe inflammatory changes appeared in the epithelial cells. In a control group of 41 matched men whose wives were pregnant in the first trimester cytological evidence of inflammation was noted only in four specimens.All men in the experimental group were treated with antibacterial drugs for two to four months, sometimes in combination with anti‐inflammatory drugs. The inflammatory changes in expressed fluids disappeared in 28 of all 37 men with cytological evidence of inflammation (75.5%). The palpatory findings were also normalized in most men who had pathological changes in the prostate and/or seminal vesicles before treatment.It is concluded that the use of exfoliative cytology enhances the accuracy of the diagnosis of inflammatory changes in the male accessory genital glands and makes the follow‐up and evaluation of treatment more objective.