bluuebunny/crossref_metadata_2025 huggingface dataset:
Animal Model of Isolated Gonadotropin Deficiency II. Morphologic Responses to LHRH Immunoneutralization
Authors: ENGLISH HUGH F. , SCHANBACHER BRUCE D. , GROSS DOUGLAS , WALKER MICHAEL F. , FALVO RICHARD E. , SANTEN RICHARD J.
Published: December 2015

Morphologic changes in the male reproductive system of mongrel dogs immunized against LHRH were quantitated using linear measurements and morphometric techniques at the light‐microscopic level. Two experimental groups (5 nonimmunized control animals and 5 actively immunized animals) were killed 12 weeks after the primary immunization. No significant differences were observed between three immunized dogs having low LHRH antibody titers (immunized‐unaffected) and the five nonimmunized control dogs. The two immunized dogs (affected) with the highest antibody titers against LHRH were characterized by atrophy and dedifferentiation of the testes, prostate, and excurrent ducts. The morphologic changes in the testes of these two dogs were striking and included an apparent arrest or significant reduction in the spermatogenic process, concurrent epithelial degeneration, and apparent diminution of Leydig cell mass. Drastic reductions in the size of the prostatic acini and epithelial cells, as well as loss of secretory granules, reflected depression of function and androgen production. Similarly, in the excurrent ducts decreases in the measured parameters and loss of regional cytoplasmic specialization denoted functional decrescence. This study demonstrates the regressive effects of LHRH immunoneutralization on the morphology of the reproductive system in the male dog and further supports the feasibility of this system as an animal model for the study of isolated gonadotropin deficiency.
Evidence for the Presence of Androgen Receptors in Purified Rat Leydig Cells
Authors: GULIZIA SALVATORE , D'AGATA ROSARIO , SANBORN BARBARA M. , STEINBERGER EMIL
Published: December 2015

Leydig cells, purified on two sequential Percoll gradients to purities of 89 ± 1%, were used to study the binding of 17‐β‐hydroxy‐17α‐memyl‐estra‐4,9,11‐triene‐3‐one(3H‐R1881). The accumulation of 3H‐R1881 in the nuclear fraction of these cells was time‐ and temperature‐dependent. Specific binding was saturable with an apparent Ka of 0.14 nM−1 and a single class of binding sites at a concentration of 721 fmol/mg DNA. A fraction of the bound radioactivity in the nuclear pellet could be extracted with 0.4 M KCl, and a portion of this extracted steroid was associated with macromolecular species. The nuclear accumulation was androgen‐specific. These data are consistent with the presence of androgen receptors in rat Leydig cells.
Heterologous Ovum Penetration Test and Seminal Parameters in Fertile and Infertile Men
Authors: WICKINGS E. JEAN , FREISCHEM CARL‐WILHELM , LANGER KLAUS , NIESCHLAG EBERHARD
Published: December 2015

Sperm penetration rates in the heterologous ovum penetration test were correlated with results of routine semen analysis in SO fertile and 50 infertile men. There was no difference in penetration rates when comparing infertile men with normal and abnormal seminal parameters, nor was any difference seen between fertile (15–83%) and infertile men (8–83%). Of the 22 infertile men with normal seminal characteristics, seven had partners with no discernible reproductive dysfunction. The penetration rates of these men (38–81%) did not differ from those of fertile men. Stepwise regression analysis of seminal characteristics, with penetration as the dependent variable, indicated that sperm count and morphology are the most important seminal parameters for fertility assessment. Discrimination analysis revealed that sperm numbers and morphologic variables provide significant information for discriminating between fertile men and infertile men with normal or abnormal seminal characteristics. Sperm penetration and motility were not indicated as important factors. The present data suggest that, in unselected male patients seeking reproductive evaluation, the sperm penetration assay did not yield any additional information on the cause of infertility.
Combined Treatment with an LHRH Agonist and Testosterone in Man Reversible Oligozoospermia without Impotence
Authors: DOELLE GREGORY C. , ALEXANDER A. NANCYE , EVANS ROBERT M. , LINDE RANDY , RIVIER JEAN , VALE WYLIE , RABIN DAVID
Published: December 2015

We have previously shown that LHRH agonist [D‐Trp6,Pro9‐NEt]LHRH (LHRHA) results in reversible oligozoospermia when given to normal subjects for up to ten weeks. A fall in plasma testosterone was accompanied by loss of libido and potency. We now report six subjects who were evaluated by semen analysis and hormone profile at two‐week intervals during ten‐week basal, 20‐week treatment, and post‐treatment periods lasting at least ten weeks. Treatment consisted of LHRHA (50 μg subcutaneously daily), and testosterone enanthate (100 mg intramuscularly every two weeks). Sperm density (mean basal 76.7 ± 8.7 ± 106/ml) fell consistently in each subject to a mean nadir of 12.3 ± 4.5 ± 106/ml (p < 0.001). This is similar to the mean nadir of 11.6 ± 5.8 ± 106/ml achieved when LHRHA was given alone. In each individual subject, sperm density returned to his basal level after cessation of treatment. No consistent changes were seen in sperm motility of morphology, or in semen volume. Libido and potency were maintained in all subjects. An additional three subjects received testosterone enanthate alone in identical dosage for 20 weeks. No change in sperm density was observed. In contrast to treatment with LHRHA alone, combination treatment produces reversible oligozoospermia without attendant change in potency.
Effects of an LHRH Agonist Analog upon Sexual Function in Male Dogs
Authors: VICKERY BRIAN H. , McRAE GEORGIA I. , BRIONES WILLIAM , WORDEN ANNE , SEIDENBERG RICHARD , SCHANBACHER BRUCE D. , FALVO RICHARD
Published: December 2015

Male beagle dogs were injected once daily with 10 μg/ kg of [6‐D‐(2‐naphthyl)alanine]‐LHRH (D‐Nal(2)6‐LHRH), a potent LHRH agonist, for periods up to 42 days, with recovery periods up to 172 days. Blood samples collected at regular intervals were assayed for LH, FSH, and testosterone; total ejaculates were collected and analyzed weekly, and animals were sacrificed at various intervals for sex organ weights and histology. The first injection of D‐Nal(2)6‐LHRH caused an acute elevation in plasma levels of LH, FSH, and testosterone, measured at 2 and 4 hours after the injection. This acute response to injection was attenuated with each successive injection and by two weeks no elevation was seen, suggesting a down‐regulation of pituitary response. Basal levels of LH and testosterone were maximally depressed by four days of treatment. Testis volume, duration of erection, ejaculate volume, sperm count, sperm motility and testis volume all declined during treatment, with sperm count significantly lowered by two weeks and ejaculation volume becoming zero by five weeks of treatment. Spermatogenesis, assessed histologically, was partially suppressed at ten days and completely suppressed by 38 days of treatment. All parameters returned to normal following cessation of treatment. Recovery time was longer for the dogs treated for 42 days than for those treated for ten days. When testosterone was supplemented during 42 days of agonist treatment, basal plasma testosterone levels were maintained at the low end of the normal range. Testosterone supplementation did not prevent pituitary down‐regulation, suppression of spermatogenesis, or the decrease in testis and epididymis weights, but prevented the decline in duration of erection. Ejaculate volume and sperm count declined more slowly with combination treatment than with agonist alone. During the decline in sperm count sperm motility was maintained with combination treatment. Injection of hCG into control and agonist treated dogs resulted in similar percentage increases in plasma levels of testosterone, although peak levels were greater in control than in treated animals. The data suggest a pituitary desensitization with this LHRH agonist in the dog but only a minor role for testicular desensitization.
Administration of Constant Low Doses of Androgens to Steers by Silastic Implant
Authors: KENNEDY RICHARD I. , RAWLINGS NORMAN C.
Published: December 2015

Yearling Hereford calves approximately 300 kg in weight were castrated and assigned to one of six treatment groups receiving subcutaneous implants (3 implants, 0.5 cm diameter by 10 cm length, 10% steroid by weight) of either androstenedione (D); testosterone (T); 5α‐androstane‐3β, 17β‐diol (3β‐diol); dihydrotestosterone (DHT); androsterone (A); or control (no steroid). Blood samples were obtained at half‐hour intervals for eight hours one day prior to, and one week after, castration. The castration‐induced elevation in FSH secretion was suppressed or modified by the DHT, T, and 3β‐diol implants. LH levels were not significantly suppressed. The T implants elevated serum T concentrations; DHT implants elevated serum 5α‐androstane‐3α, 17β‐diol (3α‐diol) and 3β‐diol, but not DHT concentrations; 3β‐diol implants elevated serum 3β‐diol concentrations. The effects of D and A implants upon serum androgen concentrations were not statistically significant, although observations in vitro suggested an adequate release rate. These data imply that T and DHT, or metabolites of DHT, suppress FSH secretion and suggest that extensive peripheral androgen metabolism occurs.
Localization of Tubulin and Microtubules of in vivo Fertilized Rabbit Oocytes
Authors: STAMBAUGH RICHARD L. , NICOSIA SANTO V.
Published: December 2015

The presence of tubulin throughout what appears to be sperm penetration tunnels of in vivo fertilized rabbit oocytes was demonstrated by both immunofluorescence and transmission electron microscopy, using fluorescein and peroxidase‐labeled antibodies, respectively. In approximately half the fertilized oocytes examined, intact microtubules were found at the point of entry of the spermatozoon into the zona pellucida, while amorphous deposits were found throughout the remainder of the tunnel, starting at the point of entry into the matrix of the corona radiata cell layer, and continuing to the perivitelline space. These continuous deposits of tubulin suggest that, in the rabbit, acrosomal microtubule‐like structures may perform a role in mammalian fertilization, possibly as an enzyme binding or delivery system, although other functions are possible. No deposition of actin was detectable in these tunnels.
Origin of a Motility Inhibitor Within the Male Reproductive Tract
Authors: DE LAMIRANDE EVE , GAGNON CLAUDE
Published: December 2015

Seminal plasma contains a motility inhibitor of demembranated reactivated spermatozoa. We investigated its origin within the reproductive tract. The highest level of inhibitor was detected in seminal vesicle fluids from the three species investigated (bull, rat, rabbit). Significant levels of inhibitor were also observed in prostatic fluids. Testes and epididymal fluids, as well as bulbo‐urethral and coagulating gland homogenates were essentially devoid of inhibitor. On a mg protein basis, the inhibitor in seminal vesicle fluid was about four times less active than the inhibitor of seminal plasma. The high level of inhibitor in seminal plasma can not be explained by the synergistic effect of the combination of seminal vesicle, prostatic and epididymal fluids. Dialysis experiments suggested that the high level of inhibitor in seminal plasma was mainly due to the presence of a dialysable activator. This activator is capable of potentiating up to four‐fold the inhibitor present in seminal vesicle fluid.
Ultrastructural Lesions in Testes from Hyperprolactinemic Men
Authors: CAMERON DON F. , MURRAY FREDERICK T. , DRYLIE DAVID D.
Published: December 2015

Testicular tissue from eight men with prolactinomas and elevated serum prolactin were evaluated by light (LM) and transmission electron microscopy (TEM). A semiquantitative assessment of testicular morphology was employed to provide a morphology index for each tissue specimen. Although in each biopsy specimen germ cell exfoliation was evident, as was abnormal structural change in the seminiferous epithelium, there was no apparent correlation with the overall degree of tissue pathology (morphology index) and the serum level of prolactin. All of the tissue displayed variably thickened seminiferous tubule walls which, when viewed by TEM, were composed of thickened laminae propriae and redundant and involuted basal laminae. Likewise, all tubules contained Sertoli cells with overt cytoplasmic degeneration, principally in the apical (adluminal) region of the cell. This was visualized, in part, as a retraction of the apical cytoplasm from periluminal spermatids and degeneration or absence of Sertoli‐germ cell junctional specializations. Sertoli‐Sertoli cell junctional complexes appeared structurally intact. Leydig cell ultrastructure was typical of normal cells and contained a variable amount of lipid and smooth endoplasmic reticulum. This also was without positive correlation with the overall degree of tissue pathology or level of serum prolactin. Our results demonstrate the variable degree of testicular pathology associated with hyperprolactinemia in man, and suggest that abnormal tubule walls and altered Sertoli cell ultrastructure are consistent findings in this abnormal endocrine condition.
Culture of Principal Cells from the Ram Epididymis: A Comparison of the Morphology of Principal Cells in Culture and In Situ
Authors: WAGLEY LYLA M. , VERSLUIS TAMARA D. , BROWN DAVID V. , AMANN RUPERT P.
Published: December 2015

A procedure was developed to isolate and culture principal cells from the initial segment, central caput, distal caput, and proximal corpus epididymidis. The morphology of cultured cells and of cells in situ was compared. Over four to ten days, principal cells cultured in a floating collagen matrix with serum‐free medium formed clusters that developed into either large sheets of columnar cells or tubular structures of cuboidal cells. Structural polarity was evident and junctional complexes reformed. The distribution and relative abundance of organelles in principal cells in situ differed depending on the region examined, and most of these regional characteristics were retained by principal cells in culture. Microvilli and membrane‐bound vesicles were less conspicuous in cultured cells. Cultured principal cells were shorter than principal cells in situ, but were of similar volume. The high purity (90%) and viability (70%) of principal cells after seven to ten days in culture, their retention of morphologic characteristics unique to the region of origin, and the formation of function units are evidence that such cultures should be valuable for studying regional differences in the function of principal cells.
Cytoplasmic Estradiol Binding Sites in Testis of Fertile and Infertile Men
Authors: SOSA A. , GINER J. , ALVA S. , SIERRA J. A. , MORALES M. , HERNÁNDEZ O.
Published: December 2015

Free cytoplasmic estradiol receptor was determined in testicular biopsies from six adults showing various primary testicular disorders, and in testicular tissue obtained at autopsy from 18 males of various ages. Estradiol receptors were found in all cases examined. Receptor concentration varied during testicular maturation and from one patient to another. The presence of the receptor at an early stage of development and the changes observed in its concentration during testicular maturation and dysfunction support the idea that estradiol may play, through its receptor interaction, an important role in the regulation of testicular steriodogenesis during postnatal human development.
Heterogeneity of Sperm Density Profiles Following 20‐Week Therapy with High‐dose LHRH Analog Plus Testosterone
Authors: RABIN Dr.DAVID , EVANS ROBERT M. , ALEXANDER A. NANCYE , DOELLE GREGORY C. , RIVIER JEAN , VALE WYLIE , LIDDLE GRANT W.
Published: December 2015

Eight normal male volunteers received an LHRH analog, 100 to 500?g daily, for 20 weeks. Testosterone enanthate, 100 mg, was given by injection every second week. Sperm density fell to 5.5 × 106/ml and to 0 in two of the subjects receiving 100?g, but was unchanged in the third. Three of the subjects who received 500?g displayed azoospermia, whereas the other two showed no significant change in sperm density. The reasons for the heterogeneity are not clear. Only one of the three nonresponders had testosterone values that were higher than the other subjects. Go‐nadotropin levels were similar in responders and nonresponders. It is possible that the respone to LHRH analog in man is determined by the extent of the reduction in LH bioactivity.
Regional Differences in Luminal Fluid Polypeptides of the Rat Testis and Epididymis Revealed by Two‐dimensional Gel Electrophoresis
Authors: OLSON GARY E. , HINTON BARRY T.
Published: December 2015

Luminal fluid samples were collected by micropuncture of the seminiferous tubule, rete testis, and defined levels of the epididymal tubule. After removal of spermatozoa by centrifugation, the supernatant fluids were analyzed by two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE) and an ultrasensitive silver staining procedure to define the sequential change in protein composition along the excurrent duct system. Fluid from each segment displayed a characteristic 2‐D PAGE map composed of numerous polypeptides. Seminiferous tubule fluid contained a wide array of polypeptides, with most concentrated in the 45 Kd to 90 Kd range, but, in contrast, rete testis fluid lacked most of these polypeptides. The major complex of rete testis fluid comigrated with serum albumin and was present in all distal segments. Other major rete testis components were not noted distally. Fluid from the caput was characterized by new major components of 30 to 37 Kd, 28 to 30 Kd, 24 Kd, and 23 Kd, each of which consisted of multiple spots of apparent isoelectric variants; all except the 30 to 37 Kd complex were present in the fluid from more distal segments. Proceeding distally, there was a temporal appearance of new polypeptides, especially in the molecular weight range below 30 Kd. Two‐dimensional PAGE analysis of detergent extracts of washed spermatozoa indicate that a specific subset of these fluid polypeptides are sperm associated.
Effects of Induced Hypoprolactinemia on Testicular Function during Gonadal Maturation in the Rat
Authors: SUESCUN MARÍA O. , GONZÁLEZ SILVIA I. , CHIAUZZI VIOLETA A. , CALANDRA RICARDO S.
Published: December 2015

We have evaluated the effects of hypoprolactinemia during gonadal maturation in the male rat. Intact 30‐day‐old rats were injected daily for 10 days with three different doses of bromocriptine (0.75, 1.5 or 3.0 mg/kg of body weight/day). At the end of the treatment period, the animals were sacrificed, serum was collected for prolactin (PRL), LH, and androgen measurements. Intratesticular testosterone and 5 α‐androstanediol (androstanediol) were measured following celite column chromatography and a specific radioimmunoassay. In addition, the production of androgens by decapsulated testes and dispersed Leydig cells was also studied in vitro. Serum levels of PRL (9.4 ± 1.9 ng/ml) were suppressed to undetectable levels in the three bromocriptine‐treated groups, whereas LH levels were not altered. All three doses of bromocriptine markedly depressed serum testosterone (plus DHT) and androstanediol. Intra‐testicular testosterone and androstanediol were diminished (25% and 35%, respectively, P < 0.05) during hypoprolactinemia. Decapsulated testes and dispersed Leydig cells from bromocriptine‐treated animals showed a significant reduction in the basal secretion of testosterone (plus DHT) and androstanediol, and in androgen responses to submaximal hCG stimulation. Maximal steroidogenic responses from bromocriptine‐treated rats were similar to controls. The present findings show that, during puberty, bromocriptine influences testicular steroidogenesis, and these effects may be partly due to changes in PRL levels. A direct effect of this dopaminergic agonist on the male gonad cannot be completely ruled out.
Stagnation of Blood in the Microcirculatory Vessels in the Testes of Men with Varicocele
Authors: CHAKRABORTY JYOTSNA , HIKIM AMIYA P. SINHA , JHUNJHUNWALA JAGADISH S.
Published: December 2015

This study reports on the stagnation of blood within the microcirculatory vessels of the testes of patients with varicocele. Both fine structural and quantitative studies were carried out on testicular biopsies from 14 men with varicocele and a control group of three men. Arterioles, capillaries, and venules were completely filled with blood in all affected testes. Enlarged pores were also noticed between the endothelial cells of these affected vessels. Lumen diameters of the arterioles were significantly decreased in the affected testis compared to controls. No change in the overall diameter of the arterioles and venules was noted. Significant thickening of the limiting membrane was also noted in the affected testis. It was concluded that the stagnation of blood in the microcirculatory vessels may cause local hypoxia and ischemia, which lead to spermatogenic disorders.
Evidence That Estrogen Regulation of Testosterone Secretion in Adult Rams Is Mediated by Both Indirect (Gonadotropin Dependent) and Direct (Gonadotropin Independent) Means
Authors: SANFORD LEE M.
Published: December 2015

Involvement of endogenous estrogen in the regulation of gonadotropin and testosterone secretion was investigated in adult rams. Groups of four rams were either passively immunized against estradiol or treated with the antiestrogen tamoxifen for 2 weeks during the breeding season (October). Circulating testosterone levels in immunized rams increased eight‐fold to supraphysiologic values as episodic elevations and baseline levels increased in magnitude; only moderate increases in LH peak frequency and magnitude occurred, and prolactin fell to undetectable levels. Tamoxifen treatment was not associated with changes in mean hormone levels, although there was a tendency toward reductions in the magnitude of episodic LH and testosterone secretion. When rams were challenged with exogenous GnRH and LH, a greater testicular endocrine response was observed in the immunized rams and the pituitary endocrine response was delayed in the tamoxifen‐treated rams. Results indicate that in the ram 1) circulating levels of estradiol provide negative feedback signals of different intensities to the testis and the hypothalamic‐pituitary axis and 2) tamoxifen exerts a mild estrogenic effect when administered at the dose of 25 mg/day.
Identification and Distribution of Pz‐peptidases A and B in Human Semen
Authors: LESSLEY BRUCE A. , GARNER DUANE L.
Published: December 2015

Human semen was fractionated into fluid, particle and spermatozoal constituents using Percoll density gradient centrifugation followed by additional separation steps. All of the fractions isolated possessed both Pz‐peptidase A and Pz‐peptidase B activity. The effects of inhibitors on the Pz‐peptidase A and B activities of all seminal fractions were similar, suggesting that hydrolysis of the Pz‐peptidase was attributable solely to these two enzymes. Estimates of the activities in intact spermatozoa indicated that 1.6 ± 0.5 mU of Pz‐peptidase A and 1.6 ± 0.7 mU of Pz‐peptidase B were present per billion spermatozoa. The predominant source of Pz‐peptidase B activity in semen was the ultra‐low density particle fraction (110,000 × g pellet from seminal plasma), which contained 86% of the recoverable Pz‐peptidase B activity. Pz‐peptidase A and B activities of fluid and particle fractions isolated from azoospermic ejaculates from vasectomized donors were similar to the activities of the corresponding fractions from normal semen. This suggested that much of the Pz‐peptidase A and B activities of semen originated in accessory gland secretions. The effects of EDTA, Zn2+ and Cu2+ on soluble Pz‐peptidase A and B activities of particle‐free seminal plasma suggested that neither was involved in the liquefaction of semen.
Prognosis of Subfertility in Men with Corrected or Uncorrected Varicocele
Authors: VERMEULEN ALEX , VANDEWEGHE MARC , DESLYPERE JEAN PAUL
Published: December 2015

To evaluate whether correction of varicocele improves fertility, pregnancy rates were compared in 115 varicocele patients consulting for infertility and having oligozoospermia, asthenospermia, or teratozoospermia, in any combination, and FSH levels within the normal range. Ninety of these patients had corrected, and 25 had uncorrected varicoceles, respectively. The value of clinical and seminal parameters for predicting the eventuality of pregnancy for varicocele patients was also studied. Although both groups were comparable in terms of duration of infertility, mean age, sperm density, motility or fertility index, cumulative pregnancy rates over 12 months were similar, whether or not the varicocele was corrected.

The value of clinical or seminal parameters, in any combination, for the prediction of outcome for varicocele patients was poor. The prognosis was poor for men with less than 15% of spermatozoa with normal morphology, FSH levels higher than the mean + 3 SD of those values found in young fathers, and a fertility index below 3. In subjects who achieved pregnancy within one year, pre‐treatment sperm characteristics were similar in both the corrected and uncorrected groups. Correction of varicocele slightly improved sperm characteristics. It seems likely that in most men with subfertility and varicocele, other factors besides venous reflux are responsible for their infertility.
α‐Glucosidase as a Specific Epididymal Enzyme Marker Its Validity for the Etiologic Diagnosis of Azoospermia
Authors: GUERIN JEAN‐FRANÇOIS , ALI HABIB BEN , ROLLET JACQUES , SOUCHIER CATHERINE , CZYBA JEAN‐CLAUDE
Published: December 2015

Azoospermic semen was obtained from 39 vasectomized men and 93 patients consulting for infertility. The latter underwent bioclinical investigations including measurement of plasma FSH and testicular biopsies. Carnitine content and α‐glucosidase activity in semen samples were measured. The activity of α‐glucosidase was determined systematically by a semiquantitative microtechnique and was verified by a spectrophotometric assay. A positive correlation was observed between carnitine and α‐glucosidase activity. Both parameters were severely diminished in semen from the vasectomized men and the patients suffering from a complete obstruction of the genital tract. Enzyme activity was the most discriminant parameter in terms of sensitivity and specificity. The measurement of α‐glucosidase in semen is a simple and sensitive method for determining the origin of azoospermia when used in conjunction with assays for plasma FSH.
Radioautographic Localization of β‐Adrenergic Receptors in the Rat Ventral Prostate
Authors: DUBÉ D. , POYET P. , PELLETIER G. , LABRIE F.
Published: December 2015

Previous studies performed with crude homogenates have demonstrated the presence of β‐adrenergic receptors in the rat ventral prostate. The precise localization of these receptors in prostatic tissue, however, has not been determined. The present study describes the localization of β‐adrenergic receptors using in vitro radioautography. β‐adrenergic receptors are present exclusively in the epithelial cells, while no receptors could be detected in the stromal cells. The silver grains mostly are associated with the apical pole of the glandular cells and are much less concentrated in the basal nuclear region of the epithelium. Very low concentrations of grains are found in the lumen of the acini. Castration caused a dramatic fall in the receptor concentration, while treatment with dihydrotestosterone reversed these effects. The specific presence of β‐adrenergic receptors in prostatic epithelial cells and their control by androgens suggest that they could play a physiologic role in androgen action in prostatic tissue. Moreover, the level and activity of β‐adrenergic receptors could be used as parameters of prostatic activity.
The Heterogeneity of Rat Androgen Binding Protein (rABP) in the Vascular Compartment Differs from That in the Testicular Tubular Lumen Further Evidence for Bidirectional Secretion of rABP
Authors: CHENG C. YAN , GUNSALUS GLEN L. , MORRIS IAN D. , TURNER TERRY T. , BARDIN C. WAYNE
Published: December 2015

Fractionation of testicular extracts and serum on a Concanavalin A‐Sepharose column resolved two peaks of immunoreactive rat androgen binding protein. The rat androgen binding protein in the first peak, designated Form I, was present in the void volume; the other, designated Form II rat androgen binding protein, was bound by the column and specifically eluted by α‐methylmannoside. In the course of studying the heterogeneity of rat androgen binding protein on Concanavalin A‐Sepharose, it was observed that the distribution of the two forms of this protein was similar in the fluid obtained by micropuncture from the seminiferous tubule and the rete testis, that is, the ratios of Form I to Form II were 1:1 and 1:1.8, respectively. By contrast, Form I rat androgen binding protein in blood, interstitial fluid, and thoracic duct lymph of adult rats was reduced relative to Form II; the ratios of Form I: Form II in these fluids were 1:4.4, 1:3.1, and 1:4.6, respectively. Since previous studies indicated that the reduced amount of Form I relative to Form II observed in the blood of adult rats was not the result of more rapid clearance of Form I, these results suggest that Form I rat androgen binding protein is preferentially secreted into the lumen of the seminiferous tubule rather than into the interstitial fluid and blood. We conclude that Sertoli cells in adult rats may partition rat androgen binding protein between the interstitial and luminal compartments of the testis based on the carbohydrate composition of this protein.
Autoradiographic Localization of Tritium‐labeled Dihydrotestosterone in Human Vas Deferens
Authors: BECKMAN WILLIAM C. , FRIED FLOYD A. , STAFFORD STEVEN J. , MICKEY DON D.
Published: December 2015

The human vas deferens was examined autoradiographically for the presence and distribution of androgen receptors. Samples of vas deferens from the region proximal to the testis and the region at the internal inguinal ring were incubated in vitro with tritium‐labeled dihydrotestosterone ([3H]‐DHT). Frozen sections of tissue were mounted on autoradiographic emulsion‐coated slides and exposed for up to three weeks to demonstrate cells with nuclear accumulations of radioactive hormone. Quantitation of autoradiograms was performed with a Zeiss Videoplan morphometric analysis system. Cells in all five tissue layers of the vas deferens were able to bind androgen receptors in the nucleus, as evidenced by superimposition of silver grains over the nuclei of cells in external, middle, and internal smooth muscle layers, as well as in epithelial and subepithelial stromal cells.
Markedly Delayed Puberty or Kallmann's Syndrome Variant
Authors: BAUMAN ARTHUR
Published: December 2015

A diagnosis of Kallmann's syndrome was made in a 25‐year‐old man. After 21 months of treatment with parenteral T, spontaneous puberty occurred at the age of 27.
Regulation of Gonadotropin Secretion in the Male: Effect of an Aromatization Inhibitor in Estradiol‐implanted, Orchidectomized Dogs
Authors: AWONIYI C. , HASSON T. , CHANDRASHEKAR V. , FALVO R. E. , SCHANBACHER B. D.
Published: December 2015

Testosterone is aromatized to estradiol in both peripheral tissues and the central nervous system. Various authors have suggested that this conversion in the male may be prerequisite for the regulation of gonadotropin secretion by testosterone. Previously, it was reported that inhibition of central nervous system aromatase caused a significant increase in plasma LH in the presence of physiologic testosterone levels (Winter et al, 1983). In order to confirm whether aminoglutethimide, the aromatase inhibitor used in our previous study, either blocked aromatization, or the action of estradiol, the following study was conducted. Fifteen male mongrel dogs were equally divided into three groups. Group 1 dogs were implanted with estradiol‐filled polydimethylsiloxane capsules only; Group 2 dogs were implanted with empty capsules and treated with 60 mg b.i.d. of aminoglutethimide; and Group 3 dogs were implanted with polydimethylsiloxane capsules filled with estradiol and treated with aminoglutethimide. Blood samples were drawn for 24 days during pretreatment, capsule implantation, castration, aminoglutethimide administration and capsule removal periods. The postcastration response of both plasma LH and FSH in dogs in groups 1 and 3 was suppressed in the presence of elevated estradiol, whereas that of Group 2 dogs was normal in the absence of estradiol. The results suggest that aminoglutethimide neither directly affects the plasma concentration of either LH or FSH nor blocks the effect of estradiol in inhibiting their release following castration. These data, taken together with our previous work, implicate aromatization of testosterone to estradiol in the control of gonadotropin secretion in the male.
The Incidence of Spermatic Granulomas and Their Relation to Testis Weight after Vasectomy and Vasovasostomy in Lewis Rats
Authors: FLICKINGER CHARLES J. , YARBRO E. SCOTT , HOWARDS STUART S. , HERR JOHN C. , CALORAS DANIEL , GALLIEN THOMAS N. , SPELL DONALD R.
Published: December 2015

The occurrence of spermatic granulomas of the vas deferens was studied in Lewis rats at intervals up to 7 months after vasectomy or vasectomy followed 3 months later by vasovasostomy. The incidence of granuloma progressed with time to involve one or both tracts in 100% of vasectomized rats. In addition, the majority of animals developed new granulomas after vasovasostomy, even though fluid flow through the reconnected vas deferens was demonstrated in vitro. When individual tracts were analyzed, the weight of the testis was related to ipsilateral spermatic granuloma formation in both vasectomy and vasovasostomy groups at 3 and 4 months after initial operation. Testes were small in the absence of a granuloma but similar to those of sham‐operated rats if a granuloma was present. The possible protective effect of spermatic granuloma formation on the testis is discussed.
Tubules in Semen of Infertile Patients Case Report
Authors: PHILLIPS DAVID M. , GOLDSTEIN MARC , ZACHAROPOULOS VANAJA R. , HEMPSTEAD PEGGY
Published: December 2015

Numerous groups of small tubules were observed in the semen of two infertile patients. These structures were about 80 nm in diameter and could be observed within larger concentric tubules. They did not resemble typical microtubules, and did not appear similar to unit membrane.
Effect of Corticosterone on Rat Epididymal Lipids
Authors: BALASUBRAMANIAN K. , ARULDHAS M. MICHAEL , GOVINDARAJULU P.
Published: December 2015

Corticosterone‐induced changes in serum hormone profiles and the lipid composition of the caput and cauda epididymidis were studied. The analysis was conducted in both unwashed and washed (free from fluids and spermatozoa) epididymal tissues. Corticosterone treatment significantly depressed serum prolactin and testosterone but gonadotropins were unaltered. In the unwashed caput region, lipid analysis showed a significant decrease in total lipids, as well as in cholesterol, phospholipid, and the phosphatidyl inositol, phosphatidyl choline, and phosphatidyl ethanolamine fractions. However, in the unwashed cauda region, the total lipid and cholesterol content was not altered while total phospholipid and phospholipid fractions were significantly decreased. On the other hand, in the washed caput and cauda regions, corticosterone induced a significant increase in total lipid, glyceride, and the mono, di, and triglyceride fractions, leaving total phospholipid and its fractions unaltered. Following 20‐day withdrawal of corticosterone treatment, all lipid classes returned to normal along with serum hormone profiles. Our findings imply that an excess of corticosterone influences epididymal lipids. These changes in the epididymal lipid pattern probably are reflected in fertility disorders in patients with glucocorticoid excess.
Reversal of Testicular Function after Prolonged Suppression with an LHRH Agonist in Rhesus Monkeys
Authors: SUNDARAM KALYAN , KEIZER‐ZUCKER ANNEKE , THAU ROSEMARIE B. , BARDIN C. WAYNE
Published: December 2015

Using subcutaneously implanted osmotic pumps, four male rhesus monkeys were continuously infused for 18 months with 100 μg/day of [(imBzl)‐D‐His6‐Pro9‐NEt]‐LHRH (LHRH‐A), a potent agonist of LHRH. After an initial increase, serum testosterone levels declined to 10% of pretreatment levels in three monkeys and the response to electroejaculation was lost. There was a decrease in testicular volume. Androgen replacement in the form of subcutaneous SILASTIC® implants releasing 7α‐methyl‐19‐nor‐testosterone acetate led to a restoration of ejaculatory response and the electroejaculates were devoid of spermatozoa. Under this treatment regimen (100 μg LHRH‐A + 100 μg androgen daily), azoospermia was essentially maintained in the three monkeys for about 8 months. Withdrawal of LHRH‐A and androgen treatment led to a complete restoration of testicular function. Serum testosterone returned to control levels and spermatozoa reappeared in the ejaculates with sperm counts reaching the normal range. Testicular volumes showed a gradual increase. These results indicate that continuous administration of an LHRH agonist together with an androgen can induce an extended period of azoospermia in rhesus monkeys. These results also show that after prolonged suppression (more than one year) of testicular function complete recovery occurs after cessation of treatment.
Cholinergic Inhibition of cAMP Accumulation in Sertoli Cells Cultured from Immature Hamsters
Authors: DAVENPORT CHARLES W. , HEINDEL JERROLD J.
Published: December 2015

Acetylcholine inhibits FSH‐induced cAMP accumulation in cultured Sertoli cells from immature hamsters. This action of acetylcholine is mimicked by muscarinic cholinergic agonists with a rank order of carbachol > acetylcholine > arecoline > pilocarpine. The carbachol‐induced inhibition of stimulated cAMP accumulation is blocked by atropine > pirenzepine but not by d‐tubocurarine, indicating an apparent muscarinic receptor similar to that found in other peripheral tissues. The fact that pirenzepine is less effective as an inhibitor of the carbachol effect than atropine further defines the muscarinic effect as of the M2 subtype. The ability of carbachol to inhibit FSH‐induced cAMP accumulation is blocked by pertussis toxin, which inhibits the action of the Ni inhibitory transducer of adenylate cyclase. These data indicate that cultured Sertoli cells from immature hamsters contain an M2 type muscarinic cholinergic receptor that is negatively coupled to the adenylate cyclase system through the inhibitory Ni transducer.
Tonic Inhibition of Adenylate Cyclase in Cultured Hamster Sertoli Cells
Authors: DAVENPORT CHARLES W. , HEINDEL JERROLD J.
Published: December 2015

Sertoli cells cultured from immature hamsters respond to FSH with a dose‐related increase in cAMP accumulation. Pertussis toxin acts synergistically with FSH to stimulate cAMP accumulation. This effect of pertussis toxin indicates that Sertoli cell adenylate cyclase is under tonic inhibition due to the activity of the Ni inhibitory transducer. The acetylcholine receptor antagonists atropine or tubocurarine, or the opiod antagonist naltrexone, have no effect on the FSH‐induced stimulation of cAMP accumulation, suggesting that neither acetylcholine nor opioids are responsible for the inhibition of Sertoli cell cyclase. While exogenous adenosine is inhibitory, adenosine deaminase augments the ability of FSH to stimulate cAMP accumulation, but not to the level of pertussis toxin. This indicates that the Sertoli cells produce endogenous adenosine that is at least partially responsible for the tonic inhibition of adenylate cyclase. Other possibilities for the tonic inhibition of cyclase include other Sertoli cell products, germ cell products, peritubular cell products or an action of FSH itself through both stimulatory and inhibitory transducers.
Sex Steroid Inhibition of LH Induction of the LH Receptor
Authors: ZIPF WILLIAM B. , HUSSEIN MOHAMED O.
Published: December 2015

Testosterone and estrogen were tested as possible mediators of the prolactin‐dependent LH induction of LH receptors in hypophysectomized adult male rats. Animals were injected s.c. with saline, prolactin (100 μg/day), or combinations of testosterone (1 mg/day) or estrogen (1 mg/day) and prolactin for 7 days following a 7‐day period of hypophysectomy. Twenty‐four hours after the last saline or prolactin injection, the animals were given a single i.p. injection of either saline or oLH (10 μg) to evaluate LH‐induced LH receptor induction. Membrane preparations from testicular homogenates were incubated with [125I]hCG as the binding ligand for determination of the receptor response and capacity. Neither testosterone nor estrogen were able to mimic the ability of prolactin to allow LH to induce the LH receptor. However, both testosterone and estrogen significantly inhibited prolactin‐mediated, LH induction of its homologous receptor.
Biochemical Studies of Metalloendoprotease Activity in the Spermatozoa of Three Mammalian Species
Authors: GOTTLIEB WAYNE , MEIZEL STANLEY
Published: December 2015

Ejaculated porcine and human spermatozoa, hamster spermatozoa from the cauda epididymidis, isolated hamster sperm heads and hamster cytoplasmic droplets contained activity that hydrolyzed the metalloendoprotease substrate ABZ‐Ala‐Gly‐Leu‐Ala‐NBA (AAGLAN). Hamster sperm heads were isolated by treating spermatozoa with proteinase K and removing sperm tails with Dowex‐50W beads. Hamster sperm activity was characterized using spermatozoa from which cytoplasmic droplets were removed by sonication and centrifugation. Porcine sperm preparations were essentially free of cytoplasmic droplets, while human sperm preparations retained somewhat more droplet material. Activity from all of these sources was inhibited by the metalloendoprotease inhibitors phosphoramidon, 1,10‐ phenanthroline, CBZ‐D‐Phe and CBZ‐L‐Phe but was not competitively inhibited by the metalloendoprotease substrate CBZ‐Ser‐Leu‐amide. The AAGLAN hydrolyzing activity found in intact spermatozoa of all three species had a pH optimum of 6.2, while the optimum of the hamster sperm cytoplasmic droplet activity was 7.0. In addition, hamster sperm preparations were inhibited by ZnCl2 and dithiothreitol, but were not affected by toluene, benzamidine or chymostatin. The AAGLAN hydrolyzing activity of hamster sperm preparations was reduced, but not eliminated, by dialysis. It is concluded that spermatozoa from all three species, hamster sperm heads and hamster cytoplasmic droplets contain metalloendoprotease activity. Furthermore, metalloendoprotease activity found in hamster cytoplasmic droplets is different from that found in spermatozoa.
Hypogonadotropic Hypogonadism and Anosmia (Kallmann's Syndrome) Associated with a Marker Chromosome
Authors: BERGSTROM RICHARD W. , HANSEN KATHRYN L. , CLARE CHARLOTTE N. , KATZ Dr.MICHAEL S.
Published: December 2015

A patient with hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) had an associated chromosomal abnormality. Evaluation of the hypothalamic pituitary axis showed undetectable basal LH and FSH and slight increases in both gonadotropins in response to GnRH. Augmented gonadotropin response to GnRH after serial subcutaneous injections of GnRH confirmed a hypothalamic defect. Additional endocrine tests failed to reveal other hormone dysfunctions. A supernumerary chromosome was detected by routine chromosome analysis. The extra genetic material was identified by differential cytogenetic banding procedures as an accessory bisatellited marker chromosome originating from either chromosome group D or G. Chromosome analyses of both parents were normal. Our results suggest that, in at least some cases, the Kallmann's phenotype may be associated with a chromosome abnormality.
Comparison of a Direct and Indirect ELISA for Quantitating Antisperm Antibody in Semen
Authors: LYNCH DONA M. , HOWE STEPHEN E.
Published: December 2015

A direct and an indirect quantitative ELISA for antisperm antibody were compared using the spermatozoa and cellfree seminal fluid of 66 infertile males. The normal concentration of sperm binding immunoglobulin was ≤ 1.5 fg Ig per spermatozoon for the indirect seminal plasma assay and ≤ 1.5 fg Ig per spermatozoon by the direct assay. Of the 66 infertile males, 21% (14/66) had elevated levels of antisperm antibody in their seminal plasma and 26% (17/66) had elevated levels bound directly to their spermatozoa. The direct correlation between the results of these assays was 94%. A simple linear regression analysis between the indirect and direct measurements of antisperm antibody resulted in a correlation coefficient of r=0.907. There was no statistically significant difference between results from the direct and indirect methods of the patients as a group. However, there was evidence of autospecificity in a small percentage of males who had elevated levels of antisperm antibody by the direct assay that was not detected by the indirect assay using pooled donor spermatozoa.
Interactions of Androgens and Prolactin in the Seminal Vesicles of Mature Bonnet Monkeys, Macaca radiata: I. Nucleic Acids and Phosphatases
Authors: ARUNAKARAN J. , ARULDHAS M. MICHAEL , GOVINDARAJULU P.
Published: December 2015

The effects of prolactin (PRL), bromocriptine, testosterone propionate (TP), dihydrotestosterone (DHT), and the combinations of these androgens with PRL or bromocriptine on nucleic acids (RNA and DNA) and phosphomonoesterases (acid and alkaline phosphatase) of the seminal vesicles of castrated mature bonnet monkeys were studied. Castration decreased body weight, and seminal vesicle organ weight, nucleic acids and acid and alkaline phosphatases. TP/DHT replacement to castrates restored body weights and seminal vesicle DNA to normal and markedly increased the weight, RNA content and acid and alkaline phosphatase activities of the seminal vesicles. PRL did not alter body weight and increased the weight of the seminal vesicles, and their RNA content and phosphomonoesterase activities. PRL + TP/DHT enhanced all parameters. Bromocriptine given alone decreased body weight and acid phosphatase. Bromocriptine given along with TP/DHT suppressed the stimulatory influence of these androgens on most of the parameters studied. The results of the present study suggest that PRL has a specific stimulatory effect on seminal vesicle growth and function, that the presence of PRL is essential for androgen action, and that PRL acts synergistically with androgens.
Measurement of Seminal LDH‐X and Transferrin in Normal and Infertile Men
Authors: ORLANDO CLAUDIO , CASANO ROSARIA , CALDINI ANNA L. , FORTI GIANNI , BARNI TULLIO , BONFANTI LAURA , SERIO MARIO
Published: December 2015

LDH‐X, an isoenzyme of lactate dehydrogenase specific for germinal epithelium activity, has been measured in the seminal plasma of infertile subjects whose infertility had different origins. In the same samples, seminal transferrin, an index of Sertoli cell function, was also measured. In this investigation, seminal LDH‐X was not detectable in the vasectomized subjects, in patients with azoospermia due to seminiferous tubular damage, nor in patients who showed a marked decrease in sperm concentration (<1 × 106/ml). In Oligozoospermic patients (sperm concentration < 20 × 106/ml) seminal LDH‐X levels were reduced to about one‐third of those found in normal controls. Seminal LDH‐X levels correlated (r = 0.7237) with total sperm count better than seminal transferrin levels (r = 0.5511), while no correlation was found between these two biochemical parameters and sperm motility, viability and morphology. To study their spontaneous variations with time, LDH‐X and transferrin were also measured in semen specimens collected monthly from five healthy men, over 1 year. In these samples (N = 60), sperm count variability (43.1%, calculated in terms of the coefficient of variation), was similar to that of LDH‐X (40.4%) and higher than for transferrin (23.0%).