Rapid oscillation of circulating gonadotropins in postmenopausal women.

The circulating levels of of radioimmunoassayable LH and FSH in three postmenopausal women were measured in samples drawn at one minute intervals for a period of 150 or 300 min in order to ascertain the existance of short term oscillation on the plasma content of pituitary gonadotropins. Radioimmunoassay methods and sampling procedures fulfilled all the requirements of quality control. Rapid and non-coincident oscillation in the plasma levels of both LH and FSH at the interval studied were observed in all cases. Statistical analysis disclosed that in addition to short-term gonadotropin fluctuation, the data successfully fit in a 120 min periodic function and the graph resembled a sine wave that was also compatible with an ultradian oscillatory pattern.

Comparative study of serum luteinizing hormone levels in human subjects as measured by radioimmunoassay and radioreceptorassay.

A rapid, precise, sensitive, and specific radioreceptorassay (RRA) for serum luteinizing hormone (LH), using a 15,000 X g pellet from bovine corpora lutea, was developed. A comparative study of the serum LH levels in human subjects as measured by this RRA and by radioimmunoassay (RIA) using the same standard preparation was then conducted. The serum LH profile throughout the entire menstrual cycle and the pituitary responsiveness to LH-releasing hormone (LH-RH) stimulation during the two phases of the cycle were studied in two normal women. In addition, LH levels in two normal postpubertal men were measured in blood samples obtained before and after LH-RH administration. Similar, although not identical, LH profiles were found in all cases by both hormone assay methods. Higher RRA-assayable LH values were obtained throughout the menstrual cycle as compared with those obtained by RIA. A significant LH-RH pituitary response in terms of LH in both RRA and RIA during the luteal phase was observed as compared with that observed during the early follicular phase. In the two normal men, the LH values obtained with RRA were higher than those obtained with RIA. It is concluded that the LH RRA is a practical and efficient tool for clinical research.

Altered testicular hormone production in infertile patients with idiopathic oligoasthenospermia.

We studied the kinetics of testicular response to human chorionic gonadotropin (hCG) in oligoasthenospermic and asthenospermic patients (OAZ-AZ). The responses of testosterone (T), androstenedione (A), 17 OH-progesterone (17OHP), and estradiol (E2) were evaluated in 60 OAZ-AZ patients and compared to those of 10 normal men. The responses of T, A, and 17OHP to hCG in the control group displayed a biphasic pattern with an initial peak at 4 hours and a second peak after 24 hours. The E2 response showed a single peak between 24 and 48 hours after hCG administration. OAZ-AZ patients had two types of T responses: group 1 (n = 40) had no first peak and group 2 (n = 20) had a normal response pattern. The response of A was similar to that of T, and the E2 response was normal in both groups. There were three types of 17OHP responses in group 1 (low, high, or normal); however, the 17OHP response was normal in group 2. Treatment of group 1 with aromatase inhibitors (aminoglutethimide or testolactone) induced an improvement of the acute T response only in patients with high or normal 17OHP response to hCG, whereas no effects were observed in patients with low 17OHP response. In group 2, the aromatase inhibitors induced no changes in the T response. These results demonstrate that in some OAZ-AZ patients (group 1, blunted T response) testicular hormone production is altered. They also suggest the presence of two enzyme blocks: one at the 17,20 desmolase level, mediated by E2, and another at early biosynthetic steps, not mediated by E2.

Plasma profile on pituitary gonadotropins and ovarian steroids in women during 17 alpha-acetoxy- 11 beta-methyl-19-nor-progesterone administration.

PIP: A study of pituitary gonadotropins and ovarian steroids in 11 healthy women during 17alpha-acetoxy-11 beta-methyl-19-norprogesterone (sc-21009) therapy is presented. 4 women received 40 mcg/day starting on Cycle Day 5 through Day 26 while 3 women received 200 mcg and 4 women received 1 mg/day also on Days 5-26. Daily blood and 24-hour urine samples were obtained for follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogens, progesterone, and pregnanediol assays. 40 mcg SC-21009 significantly increased plasma LH levels (p less than .001) through the follicular phase with only a slight increase in FSH. Higher doses of SC-21009 did not markedly change the plasma gonadotropin profile. Estrogen and progesterone levels were similar to control cycle levels at all 3 doses. These results were interpreted as demonstrating LH-FSH positive feedback mechanisms at the follicular phase during low-dose SC-21009 therapy and a lack of ovulation inhibitory activity at the doses of 40 mcg through 1 mg/day.^ieng

LH receptor in testosterone-producing ovarian tumor. In vivo and in vitro HCG-stimulated testosterone production.

The aim of the present work is to report in vivo and in vitro hormonal studies performed on a 71 year old virilized woman due to a Leydig cell tumor of the ovary. Testosterone (T), Cortisol, DHEA(s) and ACTH concentrations were determined in blood samples taken every 4 h throughout 24 h previous to surgery. T average concentration from the 6 samples was 3.3 ng/ml (range: 2.5-4.2 ng/ml). DHEA(s) was normal; Cortisol and ACTH levels were normal and their circadian rhythms were present. T value obtained during Dexamethasone administration (2 mg daily/3 days) was 2.4 ng/ml. This value was significantly higher than those obtained from postcorticoid normal women (0.3 +/- 0.1 ng/ml), suggesting an extraadrenal source. T concentration was 5.4, 6.0 and 6.6 ng/ml at 24, 48 and 72 h after hCG injection (5000 IU). After tumor removal, T values decreased progressively up to 6.0 ng/ml values, 5 days later, and remained steady on the following days. The studies performed in vitro were: determination of T in the tumor cytosol, specific binding of LH to ovarian tumor cell membrane fraction and T production in tissue culture in both with and without added hCG conditions. Normal ovarian tissue from the same patient under similar experimental conditions was used as control. The T concentration expressed as ng/mg of protein in the tumor and normal ovarian cytosol was 9.1 and 1.1, respectively. Scatchard analysis of specific 125I-hCG binding to tumor and normal ovarian cells indicated 53 pg and 28 pg of labeled hCG bound/mg of membrane protein, respectively, suggesting that this Leydig cell tumor of the ovary contained LH (hCG) receptors. The amounts of T, expressed as ng/mg of tissue/6 days, generated by tumoral and normal tissue ere 4.1 and 0.3, respectively. The addition of hCG elicited a response of 6.3 and 0.6 ng/mg protein/6 days in both preparation, respectively. These results demonstrate in vivo and in vitro hCG-stimulated T production in this particularly masculinizing ovarian tumor and suggest tumoral LH dependence.

Preliminary study of hormone determinations during aminoglutethimide therapy for advanced breast cancer.

The aim of this study is to report on Aminoglutethimide-induced hormonal modifications in advanced breast cancer. Estradiol (E2), Testosterone (T), Dehydroepiandrosterone sulphate (DHEA(s] and Aldosterone (A) were determined before, and once every two weeks during treatment with Aminoglutethimide plus Hydrocortisone in 13 menopausal women with advanced breast cancer. The patients were selected either for their E2 and P4-receptor-positive in the original tumor or in metastases or by presenting objective clinical improvement to prior endocrine treatment. On the basis of the response to treatment the patients may be classified in two groups: 1) responders (n = 7) and 2) non-responders. No significant modifications of T concentrations were obtained in group 1 until after the first 8 months of treatment. One spontaneous menopausal patient with a T basal value of 0.80 ng/ml was evaluated during 12 months of treatment. From month 8, T diminished to values below 0.30 ng/ml, indicating a direct action of Aminoglutethimide, hydrocortisone or both drugs on ovarian steroidogenesis. The results obtained from the remaining hormonal parameters, evaluated in all the cases beginning from the second week of treatment, remained unchanged throughout the entire period of study. They were as follows: 1) E2 diminished with respect to basal values between 36 and 60%, thus confirming Aminoglutethimide inhibitory effect upon peripheral aromatization; 2) DHEA(s) diminished between 80 and 90%, indicating an adrenal inhibition due to the combined effect of both drugs, and 3) Aldosterone diminished to values between 80 and 110 pg/ml, these values being within the normal lower range.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the hypothalamic-pituitary-gonadal axis in eugonadal men with type 2 diabetes mellitus.

Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a higher prevalence of hypogonadism. It still remains unclear the mechanism by which there is a relationship between hypogonadism and DM2. The objective was to evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without DM2 (normal glucose tolerance test) as control group (CG) were included. We assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii) luteinizing hormone (LH) pulsatility through blood collections every 10 min for 4 h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90 min after 100 µg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test: basal total testosterone (TT), bioavailable testosterone (BT), free testosterone (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin (SHBG) and 72 h post 5000 IU of i.m. hCG. There were no differences in age, body mass index and waist circumference between groups. Glucose was higher in the DM2 group vs. CG: 131.1 ± 25.5 vs. 99.1 ± 13.6 mg/dL, p = 0.0005. There were no difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8 ± 0.8 vs. 1.5 ± 0.5 pulses, p = 0.009. Differences in LH pulse amplitude were not found. A negative correlation was found between the number of LH pulses and glucose, r: -0.39, p = 0.03. There were no differences in the response of LH to GnRH between groups nor in the response of sexual steroids and SHBG to hCG. Patients with DM2 showed lower hypothalamic pulse frequency without changes in the pituitary response to GnRH nor testicular response to hCG. Glucose levels negatively correlated with the number of LH pulses which suggests a negative effect of hyperglycaemia in the hypothalamic secretion of GnRH.

Estudios de laboratorio de diversos parámetros orientados a tratar de dilucidar la fisiopatología del síndrome de ovarios poliquísticos. Parte 1 / Laboratory studies of various parameters aimed at trying to elucidate the pathophysiology of polycystic ovary syndrome. Part 1

Esta revisión fue realizada con el fin de evaluar nuestros resultados de laboratorio así como aquellos de la literatura que constituyen, a nuestro entender, aportes significativos en el síndrome de ovarios poliquísticos (SOP). Nuestro especial énfasis será presentar las limitaciones de las metodologías empleadas por nuestro grupo, comparativamente a las reportadas por otros investigadores. La determinación de andrógenos, en particular de Testosterona (TT), es quizá la de mayor complejidad dado que los resultados con los diferentes inmunoensayos empleados en nuestro medio producen resultados muy variables por los diferentes métodos y aún entre laboratorios que usan la misma metodología. La técnica de referencia es la cromatografía líquida en tándem con espectrometría de masa (LC-MSMS), de difícil aplicación en laboratorios de análisis clínicos debido a su alto costo y la imposibilidad de resolver numerosas muestras. En estudios previos demostramos que de los métodos habitualmente usados para evaluar la TT circulante, solo en 2 inmunoensayos los resultados obtenidos fueron satisfactoriamente validados indirectamente según el criterio del Consenso de los Centros para el Control y Prevención de Enfermedades (CDC, USA) contra LC-MSMS, los cuales fueron comparables a dicha metodología con niveles superiores a 0,5 ng/ml. El SOP puede presentar factores de riesgo aumentados para la enfermedad cardiovascular y la diabetes II. Estos factores no están debidamente categorizados en función de los distintos fenotipos del SOP. Se evaluarán los principales analitos empleados con este objetivo y los nuevos que aporten elementos de mayor especificidad en este sentido

This review was performed in order to evaluate our laboratory results as well as those of the literature that constitute, in our opinion, significant contributions in these pathophysiologies. Our special emphasis will be on presenting the limitations of the methodologies used by our group, compared to those reported by other researchers. The determination of androgens, in particular Testosterone (TT), is perhaps the most complex since the results with the different immunoassays used in our environment produce very variable results by the different methods and even between laboratories that use the same methodology. The reference technique is LC-MSMS, difficult to apply in clinical analysis laboratories because of its high cost and the inability to solve numerous samples. In previous studies, we demonstrated that, in comparison to LC-MSMS with the usual methods for evaluating circulating TT, the results obtained in only 2 immunoassays were satisfactorily validated indirectly according to the criteria of CDC against LC-MSMS, which were comparable to that methodology with levels higher than 0.5 ng/ml. PCOS may have increased risk factors for cardiovascular disease and diabetes II. These factors are not properly categorized according to the different phenotypes of PCOS. The main analytes used for this purpose will be evaluated and new ones that contribute elements of greater specificity in this sense

Estudios del laboratorio de diversos parámetros orientados a tratar de dilucidar la fisiopatología del síndrome de ovarios poliquísticos (SOP). Parte 2 / Laboratory studies of several parameters aimed to elucidate the pathophysiology of polycystic ovary syndrome. Second part

RESUMEN Diversos estudios bioquímicos adicionales a la evaluación de Testosterona total (TT), biodisponible (Tbio) y libre (TL) han sido realizados a los efectos que pudieran resultar de mayor utilidad para el diagnóstico de patologías concomitantes en el SOP, entre otros. En la hormona anti Mülleriana, cuando la concentración supera a los 3,0 ng/ml existen evidencias de que el 79% de las mismas pueden ser identificadas correctamente como SOP. El Antígeno Prostático Específico (PSA), marcador de singular importancia en pacientes con cáncer de Próstata, con técnicas ultrasensibles ha podido ser detectado en más del 50% en mujeres. En un grupo de pacientes con SOP, los niveles circulantes de PSA fueron significativamente mayores que en las mujeres sin SOP. El Kiss-1 aislado de la placenta y demostrado en otros tejidos, presenta niveles aumentados que correlacionan con la LH, TT, TL y resistencia a la insulina (RI) en adolescentes con SOP versus adolescentes sin SOP, sugiriendo que el Kiss-1 podría estar involucrado en el desarrollo del SOP en estas pacientes. Algunas pacientes con SOP están asociadas a patologías relevantes, de las cuales han sido comunicadas el aumento del BMI, mayor grado de dislipemia, adiposidad central, RI y Síndrome Metabólico (SMe). En las pacientes con un fenotipo clásico (hiperandrogenismo, alteración del ciclo menstrual y ovarios poliquísticos), estas patologías son de mayor frecuencia y severidad que en los otros fenotipos, particularmente aquellos sin hiperandrogenismo. Otras determinaciones como TNFα, interleuquinas, test de tolerancia a la glucosa, ApoB, partículas pequeñas de LDL e Inhibidor del Activador del Plasminógeno-1 han sido comunicados que podrían ser de utilidad para tener mayor sensibilidad en la definición de patología concomitantes en el SOP. Actualmente se ha comenzado a evaluar otros marcadores como el Fetuin-A; Quemerina, Nesfatina-1, Neopterina y Endocannabinoides, cuyos resultados preliminares parecerían ser un aporte importante para evaluar SMe y RI en paciente con SOP y tratar de definir su prevalencia en los distintos fenotipos de esta patología.

ABSTRACT Several biochemical studies in addition to the evaluation of total Testosterone (TT), bioavailable (bioT) and free (FT) have been performed to the effects that could be of greater use for the diagnosis of concomitant pathologies in the PCOS, among others. The anti-Müllerian hormone whose concentration when exceeds 3.0 ng/ml, there is evidence that 79% of these patients can be correctly identified as PCOS. The Prostate-Specific Antigen (PSA), a marker of singular importance in patients with prostate cancer, with ultra-sensitive techniques, has been detected in more than 50% of women. In a group of patients with PCOS, circulating levels of PSA are significantly higher than in women without PCOS. The Kiss-1 isolated from the placenta and demonstrated in other tissues, has increased levels that correlate with LH, TT, TL and insulin resistance (IR) in adolescents with PCOS respect to adolescents without PCOS, suggesting that Kiss-1 could be involved in the development of the PCOS in these patients. In some patients with PCOS, they are associated with relevant pathologies, of which the increase in BMI, higher degree of dyslipidemia, central adiposity, IR and Metabolic Syndrome (MeS) have been reported. Those that show a classic phenotype (hyperandrogenism, alteration of the menstrual cycle and polycystic ovaries) these characteristics are of greater frequency and severity than in the other phenotypes, particularly those without hyperandrogenism. Other determinations such as TNFα, interleukins, glucose tolerance test, ApoB, small particles of LDL and Plasminogen Activator Inhibitor-1 have been reported that could be useful to have greater sensitivity in the definition of concomitant pathology in the PCOS. Currently, other markers such as Fetuin-A, Chemerin, Nesfatin-1 Neopterin and Endocannabinoids have been evaluated. The preliminary results suggest to be an important contribution to define MeS and IR in patient with PCOS and to try to determine its prevalence in the different phenotypes of this pathology.

Cosecretion of glycosylated prolactin and non-glycosylated prolactin from childhood to the end of puberty.

BACKGROUND: Glycosylated prolactin (G-PRL) is considered as the major post-translational modification of prolactin (PRL) showing reduced lactotropic and mitogenic activities compared to non-glycosylated prolactin (NG-PRL). AIM: To evaluate the evolution of G-PRL in normoprolactinemic children and adolescents and to analyze possible variations in glycosylated/total prolactin (T-PRL) ratios. METHODS: T-PRL, G-PRL and NG-PRL were evaluated in 111 healthy female and male children and adolescents (4.1-18 years), classified as group 1 (Tanner I), group 2 (Tanner II-III) and group 3 (Tanner IV-V). G-PRL and NG-PRL were identified by chromatography on concanavalin-A-Sepharose. RESULTS: G-PRL/T-PRL (median-range): females, group 1: 0.59 (0.17-0.77), group 2: 0.56 (0.31-0.78), group 3: 0.60 (0.38-0.79); males, group 1: 0.64 (0.39-0.80), group 2: 0.61 (0.24-0.79), group 3: 0.62 (0.35-0.90); the p value is not significant among the different groups in both genders. G-PRL/T-PRL ratios do not change when comparing low (first quartile) versus high (third quartile) T-PRL levels in the different groups. CONCLUSION: Our study would appear to support cosecretion of G-PRL and NG-PRL from childhood to the end of puberty. Such cosecretion would not be dependent on sex steroid levels. It is important to point out that puberty does not change the proportions of G-PRL and NG-PRL.

Radioimmunoassays of human luteinizing and follicle-stimulating hormones using the same radioactive tracer.

The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) provides the hFSH-I-3 preparation, to be employed as a tracer in the radioimmunoassay (RIA) of human follicle-stimulating hormone (hFSH). The contaminating LH contained in that preparation led us to study whether the iodination of such a material could render it a suitable tracer for RIA of both LH and FSH. hFSH-I-3 was labelled with 125I by the chloramine-T method and was further purified on Sephadex G-75 column. The LH-RIA was performed using this preparation and anti-LH at a final dilution of 1:37,500, with a sensitivity of 3 mIU LH/ml (2nd international reference pattern). The method was validated by comparing the LH values obtained in different serum samples with those obtained using the standard RIA (125I-LH/anti-LH); the correlation coefficient (r) was equal to 0.9988. No LH overestimation due to the putative cross-reaction with FSH was found. This was demonstrated by testing serum samples containing high (greater than 100 mIU/ml) and low (less than 10 mIU/ml) concentrations of FSH before and after the treatment with anti-LH. Under these conditions, serum samples from postmenopausal women, pregnant women, normal men and women in basal conditions and after the LH-RH administration, and from a patient with Klinefelter's syndrome, were evaluated. In conclusion, NIDDK 125I-hFSH-I-3 can be used as a tracer for the radioimmunological quantitation of both hLH and hFSH, which results not only inexpensive, but also allows to reduce the amount of the stored radioactive materials.

Failure of the müllerian regression factor in two patients with complete androgen insensitivity syndrome.

The present paper describes the histological and endocrinologic features of 2 subjects with 46,XY karyotype affected by complete androgen insensitivity syndrome (AIS) with müllerian structures. Both patients had fallopian tubes, but only one had also uterus and presented a seminoma. Serum levels of luteinizing hormone, testosterone and estradiol were high or in the upper part of normal limits, whereas levels of follicle-stimulating hormone were normal. The association between AIS and the presence of müllerian structures observed in these 2 patients might be explained by an impaired synthesis of müllerian regression factor or by a failure in its mechanism of action.

Prolactin, estriol and progesterone levels in frequent blood samples throughout normal pregnancy (lack of prolactin pulsatile secretion).

The aim of this paper was to study the episodic fluctuations of circulating prolactin (PRL), estriol (E3) and progesterone (P4) concentrations throughout pregnancy. We examined 24 pregnant women; 21 were between the 28th and 40th week of gestation, and the other 3 in the 12th, 16th and 20th week of gestation. Blood samples were drawn every 5 min for half an hour, and every 15 min for one and a half hour. Blood samples were taken in two and three different weeks of gestation in 11 and 2 of the cases, respectively. Two normal non-pregnant women were also studied and used as controls. PRL, E3 and P4 were determined by radioimmunoassay in all the samples. The coefficients of variation of PRL values were 40 and 22.6%, respectively, in the two control women, 8, 12 and 9.8% in the pregnant women studied at the 12th, 16th and 20th week of gestation, respectively, while in the 21 cases studied during the third trimester the coefficient of variation was 8 +/- 3% (mean +/- SD). The coefficients of variation of the values obtained for E3 and P4 in women studied in he third trimester were 26 +/- 15 and 16 +/- 6% (Mean +/- SD), respectively. There was an increase in the average concentration of the three hormones in all the cases at two or three different weeks. We can conclude that E3 and P4 have a pulsatile secretion pattern throughout pregnancy, and that PRL looses its pulsatile secretion as from an early gestational age. Our results suggested that central mechanisms regulating PRL episodic fluctuations were altered during pregnancy.

Suprahypophyseal dysfunction in a patient with asexual ateleiosis.

The neuroendocrine function of a 19 years old female dwarf with primary amenorrhoea and lack of sexual development (asexual ateleiosis) was studied. Undetectable fasting plasma levels of growth hormone (GH) and a lack of response to three different provocative stimuli was observed. Oestrogen administratin did not modify the GH response. Thyroid and adrenal function were within normal limits. Undetectable plasma levels of immunoreactive oestradiol and lack of oestrogenic activity in vaginal smears indicated absence of ovarian function. Low levels of circulating gonadotrophins with a significant rise after synthetic LH-RH administration was demonstrated, while clomiphene citrate failed to induce ovulation. Following 6 months of continuous GH administration a significant increase in the growth rate was evident, whereas no pubertal development was observed. These data are interpreted as demonstrating the suprahypophyseal origin of the sexual infantilism in a patient with inappropriate GH secretion. It is suggested that a combined deficiency of LH-RH and GH-RH may account for the aetiology of this disorder.

Sleep-dependent hyperprolactinemia and Corpus luteum pathogenesis.

The results obtained in wake and sleep conditions by PRL determinations performed in 6 normoprolactinemic infertile women with luteal phase deficiency (LPD) are reported. Infertility was apparently due to LPD. PRL levels were determined by RIA in blood samples collected at 20-min intervals from 18(00) to 08(00). LPD has been previously demonstrated by endometrial biopsy, basal temperature and circulating progesterone determinations. PRL levels were also determined in 5 normal women used as control subjects under the same experimental conditions. The results obtained, expressed as means +/- SD of LPD vs. control group, were 15.9 +/- 4.6 vs. 11.6 +/- 3.3 ng/ml (p greater than 0.1) in wake conditions and 31.9 +/- 5.9 vs. 21.4 +/- 5.7 ng/ml (p less than 0.01) in sleep conditions. PRL values during the highest pulse (HP) in sleep and wake conditions were 20.9 +/- 5.2 vs. 17.0 +/- 3.3 ng/ml (p less than 0.1) and 51.1 +/- 17.1 vs. 34.3 +/- 2.4 ng/ml (p less than 0.01), respectively. In 2 out of the 6 patients mean PRL values were 22.0 and 26.5 ng/ml during sleep, and 26.0 and 33.0 ng/ml during HP. These values were not statistically significant when compared with those obtained in the control group. The results obtained show that 4 out of the 6 patients with LPD and normal PRL levels in wake conditions had sleep-dependent hyperprolactinemia due to the pulses with a more significant amplitude. These findings suggest that in some cases sleep-induced hyperprolactinemia might be involved in LPD pathogenesis.

Serum luteinizing hormone pulsatility and intratesticular testosterone and oestradiol concentrations in idiopathic infertile men with high and normal follicle stimulating hormone serum concentrations.

The purpose of the study was to evaluate pulsatile luteinizing hormone (LH) release and intratesticular concentrations of testosterone and oestradiol in infertile men, to determine if alterations in gonadotrophin secretion are associated with changes in the testicular concentrations of steroids. Patients with idiopathic oligo/azoospermia were divided into a high follicle stimulating hormone (FSH) group (n = 5) and a normal FSH group (n = 6). Blood samples were taken every 15 min for 6 h to determine LH, FSH, testosterone, oestradiol, sex hormone binding globulin, bioactive LH and bioavailable testosterone. The patients underwent a bilateral testicular biopsy for histological assessment and to determine testosterone and oestradiol concentrations. Serum measurements were compared with those of seven fertile men. The high FSH group had a higher concentration of serum LH and oestradiol than normal men (P < 0.01) and showed a lower frequency of LH pulses than the normal FSH group and control men (P < 0.01). Intratesticular oestradiol was higher in the high FSH group (P < 0.001), with a lower testosterone/oestradiol ratio (P < 0.01). Patients showed a negative correlation between the serum testosterone/LH ratio and FSH (r = -0.75; P < 0.01) and a positive correlation between the testicular oestradiol concentration and serum FSH (r = 0.86; P < 0.01). The histopathological examination only showed a smaller tube diameter in the high FSH group (P < 0.05). These data seem to indicate that a higher intratesticular concentration of oestradiol with a lower testosterone/oestradiol ratio in the high FSH group could have a deleterious effect on spermatogenesis.

Regulatory effects of steroids on the pituitary response to LH-RH.

PIP: The effects of continuous intravenous administration of luteinizing hormone-release hormone in conjunction with physiological or pharmacolog ical doses of estradiol (E2), progesterone (P), 17alphaOH-progesterone (17-P), 20alphaOH-progesterone (20-P), chlormadinone acetate (CA), testosterone (T) and 5alpha-dihydrotestosterone (5-DHT) on pituitary response was evaluated in normal and postmenopausal women, normal men, and 1 patient with Klinefelter's syndrome. An all subjects, except the Klinefelter's syndrome patient, 132 mcg/hour/6 hours of E2 blocked the pituitary response to LH-RH, although a dose of 6.6 mcg/hour/6 hours was not markedly effective. None of the progestational steroids blocked the pituitary response to LH-RH. However, the dual administration of CA with E2 antagonized the pituitary response in normal and postmenopausal women. 600 mcg/hour/6 hours of T partially inhibited the pituitary resp onse in men, but had little effect on postmenopausal women and the Klinefelter's syndrome patient. The pituitary response to LH-RH was not inhibited by 5-DHT. The results indicate that sex steroids can modulate the hypothalamic-pituitary axis, though estradiol by itself does not appear to increase the pituitary response to LH-RH since it is not solely responsible for the pituitary responsiveness to LH-RH at the mid-luteal phase.^ieng