Recombinant human follicle-stimulating hormone administration increases testosterone production in men, possibly by a Sertoli cell-secreted nonsteroid factor.

We previously showed that recombinant human FSH (R-FSH) in males increased the testosterone (T) concentration in spermatic venous blood (SB). To investigate the effect of R-FSH on spermatic steroid levels and the action of steroid- and LH-free SB on isolated Leydig cells, nine normospermic males were studied during spermatic cord surgery. Peripheral blood and SB samples were collected before and 30 min after iv administration of 150 U R-FSH to measure LH, FSH, T, estradiol, 17alpha-hydroxyprogesterone, and sex hormone-binding globulin, and in SB, androstenedione (delta4) and dehydroepiandrosterone (DHEA) were also measured. LH bioactivity was assessed by in vitro production of T in isolated Leydig cells. The actions of R-FSH and SB (steroid and LH free) were analyzed in the bioassay. Data are expressed as the mean +/- SE. FSH in peripheral blood and SB increased by 411% and 477% after R-FSH administration. R-FSH induced a significant increase in spermatic T (basal vs. 30 min, 326.4 +/- 98.5 vs. 732.4 +/- 152.8 ng/mL; P < 0.047) and in spermatic estradiol (289.5 +/- 66.9 vs. 535.6 +/- 83.4 pg/mL; P < 0.036). The T/delta4 ratio (36.9 +/- 9.2 vs. 74.5 +/- 13.3; P < 0.019) and the T/DHEA ratio (10.8 +/- 1.1 vs. 22.4 +/- 4.9; P < 0.024) increased significantly. In isolated Leydig cells, R-FSH did not change T production, but the SB (steroid and LH free) after R-FSH administration induced an increase in T production (3.3 +/- 0.6 vs. 4.9 +/- 0.6 ng/tube; P < 0.04). LH-like activity was found in a more than 50,000-Da fraction after centrifugation in Amicon filters, even in the presence of anti-LH. These results suggest that R-FSH increases the production of T by Leydig cells through a Sertoli cell-released nonsteroid factor with a molecular mass greater than 50 kDa. The increase in the T/delta4 and T/DHEA ratios indicates that this factor would act by amplifying the LH response through the delta5 pathway and the 17beta-hydroxysteroid dehydrogenase enzyme.

Gynecomastia as a familial incomplete male pseudohermaphroditism type 1: a limited androgen resistance syndrome.

Four postpubertal 46 XY male patients with an inherited form of bilateral gynecomastia were studied to delineate the nature of the disease. Normal serum FSH and moderately elevated serum LH with concomitantly increased circulating levels of testosterone (T) and estradiol (E2) were found persistently in all cases in blood samples drawn at frequent intervals. LRH pituitary stimulation resulted in an exaggerated LH response and a normal FSH response. Chronic administration of T-cyclopentylate failed to decrease serum LH levels. The peripheral conversion rate of androstenedione to estrone was within normal limits. All patients had low ejaculate volumes with relatively normal spermatozoa counts. Testicular biopsies revealed normal Leydig cells and complete spermatogenesis. Urological examination disclosed that the prostate gland was extremely small. The breast tissue demonstrated the presence of tubular structures as well as the specific binding of [3H]T and [3H]dihydrotestosterone (DHT), which was inhibited by nonlabeled T, DHT, E2, and progesterone, but not by cortisol. The pedigree suggested a recessive X-linked inherited trait. A patient with a nonfamilial form of gynecomastia served as a control in all studies. These data were interpreted as demonstrating that this inherited type of gynecomastia represents the mildest expression of the androgen resistance syndromes and, therefore, belongs to the type 1 form of familial incomplete male pseudohermaphroditism.

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.

Hypothalamic-pituitary-gonadal function in patients with myotonic dystrophy.

Gonadal function was studied in three post-pubertal siblings (two male and one female) and one unrelated male patient with myotonic dystrophy. The diagnosis was confirmed in all cases by electromyography and muscle biopsy. Basal levels of plasma immunoreactive LH, FSH, testosterone, and estradiol were measured. Hypothalamic, pituitary, and gonadal reserve and responsiveness were evaluated by clomiphene, LHRH, and HCG tests. Histologic examination of gonadal biopsies was also performed. The results showed that gonadal failure present in the four patients had different characteristics. In the same family, hypothalamic amenorrhea was observed in the female patient, and hypothalamic eunuchoidism and hypergonadotropic hypogonadism with marked tubular and leydig cells failure in the male patients. The non-related male patient had hypergonadotropic hypogonadism with tubular failure but with a compensatory leydig-cell hyperplasia. These data are interpreted as demonstrating different expressivity of the hypogonadism associated with the same inherited muscle disease.

Familial incomplete virilization due to partial end organ insensitivity to androgens.

A 16-yr-old 46 XY individual with a familial incomplete male pseudohermaphroditism closely resembling the syndrome described by Gilbert-Dreyfus et al. was studied. The patient's habitus was masculine despite the presence of a small phallus, pseudo-vaginal perineal hypospadias, bifid scrotum, gynecomastia, and diminished virilization. Blood samples obtained at 20-min intervals were submitted to hormone analysis. Episodic fluctuations of plasma gonadotropins with mean values of LH above the normal male range and FSH within normal limits were observed. Moderately elevated plasma testosterone and increased plasma estradiol also showed episodic oscillations. The administration of LH-releasing hormone resulted in a significative increase of plasma LH and FSH. Testicular biopsy revealed the presence of seminiferous tubules with few spermatogonia and no spermatocytes, and normal sertoli and interstitial cells. Gonadal stimulation with hCG for 4 consecutive days induced a significative increase of plasma testosterone and estradiol. The daily administration of 50 mg of testosterone propionate for 3 days neither depressed the circulating levels of gonadotropins nor modified the pulsatile pattern of gonadotropins release. Administration of testosterone and 5alpha-dihydrotestosterone propionate failed to diminish plasma LH and FSH levels. Testosterone administration for 10 weeks also failed to induce virilization. These results are similar to those observed in patients with testicular feminization syndrome, and the underlying abnormality involves a partial defect of the mechanism of action of testosterone rather than decreased androgen biosynthesis. According to a recently proposed classification this individual corresponds to the type 1 incomplete male pseudohermaphroditism.

The Stein-Leventhal syndrome: a neuropituitary disorder.

Hypothalamic and pituitary gonadotropin function and responsiveness in four patients with well-documented Stein-Leventhal syndrome were studied. All patients were of reproductive age and had had menstrual disorders since menarche. Estrogen production was assessed by measuring the circulating levels of immunoreactive estradiol, by vaginal smears, and by the progestogen-induced menses test. Gonadotropin function was evaluated by measuring the serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood samples obtained at 15-minute intervals for 150 minutes. Pituitary gonadotropin reserve and responsiveness were studied by giving an intravenous bolus of synthetic LH-releasing hormone (LH-RH) and measuring the circulating gonadotropin levels before and after the injection.

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.

Hypothalamic-pituitary-testicular axis and seminal parameters in hyperthyroid males.

Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyperthyroidism on hypothalamic-pituitary-testicular axis and on spermogram parameters, 25 male patients (19-47 years old) suffering from active Graves' disease were studied. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were measured before and after administration of 100 microg GnRH plus 200 microg thyrotropin-releasing hormone (TRH). Testosterone (T), estradiol (E2), and 17-hydroxyprogesterone (17-OHP) were determined before and after 5000 IU human chorionic gonadotropin (HCG) administration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), androstenedione and bioavailable testosterone (bioT), and bioavailable estradiol (bioE2) were also measured. Spermograms according to World Health Organization (WHO) criteria were determined in 21 patients. Hormonal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia, and low testicular volume were found in 12, 6, and 3 hyperthyroid patients. Mean basal LH was significantly higher than the control group (7.8 +/- 4.7 vs. 5.0 +/- 1.9 mIU/mL, respectively, p < 0.02), with hyperresponse to GnRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 +/- 3.4 and 12.0 +/- 2.8 ng/mL, p < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T: 9.3 +/- 3.3 vs. 5.4 +/- 1.6 ng/mL, p < 0.005; E2: 62.2 +/- 25.2 vs. 32.1 +/- 11.0 pg/mL, p < 0.005; 17-OHP: 2.4 +/- 0.9 vs. 1.1 +/- 0.5 ng/mL, p < 0.001; SHBG: 102.3 +/- 37.3 vs. 19.0 +/- 5.0 nmol/L, p < 0.01). The maximal increment of T and 17-OHP after HCG was lower in hyperthyroid patients than in normal men (p < 0.019 and p < 0.001, respectively). Basal bioT was lower in patients than controls (1.7 +/- 0.8 and 3.1 +/- 1.9 ng/mL, p < 0.02). The following incidence of abnormal semen parameters was found: asthenospermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alterations was observed in the limited number of patients evaluated. Our results confirm that hyperthyroidism causes marked alterations of the gonadotropic and PRL axis and dramatically affects spermatic function. BioT measurement was useful to identify hypoandrogenism in these patients in spite of the high concentration of total testosterone. The restoration of most semen parameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.

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.