Evidencias en indicaciones de la progesterona / Evidence in progesterone prescription

Resumen ANTECEDENTES: la progesterona es una hormona esteroide con participación en la ovulación, implantación, embarazo y regulación de la función uterina durante el ciclo menstrual y de otros órganos, como la glándula mamaria. Por su mecanismo de acción, la progesterona está indicada en distintos padecimientos ginecológicos y obstétricos: síndrome premenstrual, amenaza de aborto, parto pretérmino, hemorragia uterina disfuncional y mastalgia relacionada con el ciclo menstrual. OBJETIVO: evaluar la seguridad y eficacia de la progesterona en pacientes con: síndrome premenstrual, amenaza de aborto y de parto pretérmino, hemorragia uterina disfuncional, mastalgia y terapia hormonal en la menopausia. METODOLOGÍA: revisión sistemática de la evidencia científica acerca de las distintas indicaciones de la progesterona. RESULTADOS: se encontraron 92 artículos de los que se seleccionaron 41 para revisión. CONCLUSIONES: la evidencia clínica evaluada acerca de las indicaciones de la progesterona demuestra ventajas en eficacia y seguridad en los diferentes esquemas.

Abstract BACKGROUND: Progesterone is a steroid hormone involved in ovulation, implantation, pregnancy and regulation of uterine function during the menstrual cycle and other organs such as the mammary gland. Because of its mechanism of action, progesterone is indicated in different gynecological and obstetric conditions: premenstrual syndrome, threatened abortion, preterm birth, dysfunctional uterine bleeding and mastalgia related to the menstrual cycle. OBJECTIVE: To evaluate the safety and efficacy of progesterone in patients with: premenstrual syndrome, threatened abortion, preterm birth, dysfunctional uterine bleeding, mastalgia and hormone therapy in menopause. MATERIAL AND METHODS: Systematic review of scientific evidence about different indications of progesterone. RESULTS: We found 92 articles from wich 41 were selected for review. CONCLUSIONS: The clinical evidence evaluated on different indications of progesterone demonstrates advantages in efficacy and safety in different regimens.

Expression of connexin43 in mouse Leydig, Sertoli, and germinal cells at different stages of postnatal development.

Connexin 43 (Cx43) is the most abundant and ubiquitously distributed gap junction protein in testicular cells. Lack of Cx43 expression results in male infertility. We investigated whether Cx43 is expressed and regulated in Leydig, Sertoli and germinal cells at different stages of postnatal development. Cx43 was detected using three different antibodies shown by immunoblotting to be highly specific. At different postnatal ages Cx43 localization was compared in serial or double labeled testicular cryosections with immunocytochemical distribution of steroidogenic enzyme, 3 betahydroxysteroid-dehydrogenase (3betaHSD), Mullerian inhibitory hormone (MIH), and germinal nuclear cell antigen (GNCA1), which are specific markers of interstitial Leydig, Sertoli and germinal cells, respectively. In the interstitium, round cell clumps (RCC) with lipid droplets positive for 3betaHSD and Cx43 were frequently found at intertubular areas at birth and Cx43 was mainly localized at cell membrane appositions. From day 3, the number and size of 3betaHSD-positive RCC started to decrease, and reached a minimum at 7-14 dpp; Cx43 expressed by them is progressively downregulated. From day 21 an increase in the size and number of RCC positive for Cx43 and 3betaHSD was found that continued at 24, 26 and 28 days and reached a maximum at 35 and 60 dpp. Biphasic expression of interstitial Cx43 and 3betaHSD was also found to be positively and temporally correlated with fluctuations in intratesticular testosterone content at all ages studied. In the seminiferous cord (SC), Cx43 was expressed at birth between adjacent Sertoli cells (MIH positive) localized at the periphery, as well as in their cytoplasm projections that surround centrally localized gonocytes. From days 3 to 7, Cx43 labeling increased in Sertoli cells mainly at their apical border. At day 14, Cx43 distribution in Sertoli cells changed from apical to basal in parallel to migration of germinal (GNCA1-positive) cells from the periphery to the center of the SC. At all these ages, Cx43 was also localized at cell borders between Sertoli and germinal cells. In conclusion, this study demonstrates that Cx43 in Leydig cells is regulated during postnatal development in an age and functional dependent manner. In the tubule, it is demonstrated that Cx43 is modulated in Sertoli cells during the neonatal and prepubertal period. We also provide evidence for the first time that Cx43-gap junctions communicate between Sertoli and germinal cells before and during the first wave of spermatogenesis.

Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in postmenopausal Mexican women.

OBJECTIVE: To assess the serum concentrations of estradiol (E2), estrone (E1), gonadotrophins, sex hormone-binding globulin, and lipids, and to determine degree of symptom relief after subcutaneous implantation of 25 mg estradiol in postmenopausal Mexican women. DESIGN: Fifteen postmenopausal, hysterectomized women participated in an open, observational study. Blood samples were obtained before implantation and at regular intervals during a study period of 24 weeks. Climacteric symptoms were evaluated by means of the Greene climacteric scale. Wilcoxon's test was performed on the paired results of pre-and postimplantation values. RESULTS: Serum concentrations of E2 obtained after implantation were fairly constant, remaining within the early follicular range for the entire study period of 24 weeks, and were associated with significant symptom relief. A physiological, premenopausal E2:E1 ratio was achieved. No significant metabolic changes occurred. Side effects were estrogenic in nature and no removal of implant was required. CONCLUSIONS: Subcutaneous implantation of 25 mg estradiol results in physiological, premenopausal estrogen concentrations in most women and is associated with considerable symptom relief without inducing significant adverse metabolic effects.

Insulin gene expression pattern in rat pancreas during the estrous cycle.

Sex steroid hormones influence insulin homeostasis and glucose metabolism, estradiol (E2) and progesterone (P4) induce changes in both fasting and postprandial insulinemia in rodents, however, insulin gene expression during estrous cycle is unknown. The aim of the present study was to determine an insulin gene expression pattern during the estrous cycle in the rat. Groups of 6 adult rats in each day of the estrous cycle were used. Serum P4, E2, testosterone (T) and insulin concentrations were determined by radioimmunoassay (RIA). A Northern blot analysis was performed to assess insulin gene expression in pancreatic tissue. We found a marked variation in insulin gene expression during the estrous cycle. The highest insulin expression was observed during the proestrus day. Interestingly, E2 and P4 but not T levels were correlated with changes in insulin mRNA content. The variations in serum insulin during the cycle were correlated with its mRNA content in pancreas. The overall results showed variations in serum insulin and insulin gene expression during estrous cycle of the rat that correlated with circulating E2 and P4 levels.

Testosterone effect on insulin content, messenger ribonucleic acid levels, promoter activity, and secretion in the rat.

Coexistence of hyperinsulinemia and hyperandrogenism in women has been frequently described. Most of the studies addressing this issue have focused on the mechanisms by which insulin produces hyperandrogenism. In the present study, we analyzed the effects of testosterone in vivo and in vitro upon insulin gene expression and release in the rat. Our studies demonstrate that testosterone increases insulin messenger RNA (mRNA) levels in vitro as well as in vivo. In both prepuberal and intact adult rats, serum testosterone concentrations were positively correlated with insulin mRNA levels and insulin concentration in serum. Testosterone deprivation after gonadectomy decreased both insulin gene expression and serum insulin concentration. Insulin mRNA levels were partially restored after 3 days of testosterone administration and serum insulin was 80% and 27% above baseline values at 5 and 7 days posttreatment. Primary cultured pancreatic islets treated with the sexual steroid increased about 80% insulin mRNA, as well as protein, and release. In transfected islets, testosterone increased the activity of the -410 bp rat insulin promoter I by 154%. These data demonstrate that testosterone has a direct effect upon pancreatic islet function by favoring insulin gene expression and release.

Reactivity of different LH and FSH standards and preparations in the world health organization matched reagents for enzyme-linked immunoassays of gonadotrophins.

The immunoreactivity of various LH and FSH calibration standards and recombinant preparations in the enzyme-linked immunoassay (EIA) systems for gonadotrophins developed for the Special Programme of Research in Human Reproduction of the World Health Organization (WHO) were compared. The preparations tested included three LH and two FSH pituitary standards (calibrated against LH 80/552 and 68/40 and FSH 78/549 respectively) provided with the EIA or radioimmunoassay WHO matched reagent kits, the pituitary preparation LER-907, and recombinant human LH (rhLH) and FSH (rhFSH). Simultaneous curve fitting of the EIA dose-response curves revealed no significant differences among the slopes generated by the WHO LH standards and LER-907; in contrast, no parallelism was found between the curves of rhLH and the pituitary-derived LH standards. No significant differences were found among the slopes of the curves elicited by the pituitary and recombinant FSH preparations. Each LH preparation exhibited a high degree of charge heterogeneity. Considerable variations in charge isoform distribution among the WHO LH standards, rhLH and LER-907 were also evident. In contrast, the FSH preparations were less heterogeneous and exhibited minor differences in charge distribution. Despite the existing differences in charge isoform distribution, all the pituitary-derived preparations as well as rhFSH seem appropriate for using as calibration standards in this particular EIA system.

Hypothalamic dopaminergic tone and prolactin bioactivity in women with polycystic ovary syndrome.

BACKGROUND: The present study was carried out to investigate the functional significance of the reduced dopaminergic tone in subjects affected with polycystic ovary syndrome (PCOS). METHODS: Our group evaluated the response of pituitary PRL, LH, FSH, and TSH to the administration of a single 10-mg oral dose of the dopamine (DA) receptor antagonist metoclopramide in lean (n = 7) and obese (n = 8) PCOS women and in 11 regularly cycling age- and weight-matched controls (six lean and five obese). In addition, circulating PRL bioactivity was evaluated by its mitogenic activity on a lymphoma cell bioassay. RESULTS: Oral administration of metoclopramide resulted in a significant increase in serum PRL in all subjects; however, the highest increments, regardless of body mass index (BMI), were observed in control women (p <0.005). Measurements of PRL mitogenic activity on the Nb2 lymphoma cell bioassay revealed a significant increase in the bioactive/immunoreactive (B/I) ratio of PRL under basal and stimulated conditions in obese PCOS subjects (p <0.05). Mean fasting glucose/insulin and glucose/insulin-AUC ratios were significantly lower (p <0.001) in obese PCOS when compared with all other groups. CONCLUSIONS: These data support the existence of low DA hypothalamic tone in PCOS women that is likely involved in the inappropriate LH and PRL secretion frequently seen in this syndrome. In addition, our results suggest changes in PRL bioactivity in obese PCOS that may play a role in the development of hyperinsulinemia; however, whether PRL has a functional significance in the development of the metabolic disturbances frequently seen in PCOS remains to be elucidated.

Synthesis of steroids in pancreas: evidence of cytochrome P-450scc activity.

In pancreas, the activities of several sex steroid-transforming enzymes have been reported. Data have been obtained in perfused organs, total tissue homogenates, and subcellular organelles. These data, concurrent with the description of the presence of ligand-regulated steroid receptors, as well as the sexually dimorphic behavior of some pancreatic tumors, are clear evidence in support of the participation of steroid hormones in the pancreatic function. In this study, the steroidogenic ability of the pancreas was demonstrated by two different methods: (a) in tissue homogenates, by the identification of cytochrome P-450scc gene (CYP11A) transcripts after reverse transcription-polymerase chain reaction amplification (RT-PCR); and (b) in isolated mitochondria by the glutethimide-dependent inhibition of cholesterol-pregnenolone biotransformation. The results obtained in a series of independent experiments showed that (a) the pancreatic tissue possessed transcriptional activity of the CYP11A gene, although to a lesser extent than the typical steroidogenic tissues, and (b) isolated mitochondria obtained from the pancreas were able consistently to synthesize pregnenolone; furthermore, the addition of the specific inhibitor aminoglutethimide (AMG) blocked its synthesis. On the whole, these findings are interpreted as clear evidences of the activity of the cytochrome P-450scc enzymatic complex (P450scc), responsible for the transformation of cholesterol into pregnenolone and considered the first and limiting step in steroid biosynthesis.

A reliable endocrine test with human menopausal gonadotropins for diagnosis of true hermaphroditism in early infancy.

In true hermaphroditism diverse phenotypes and karyotypes are found; there are no distinctive laboratory features that can distinguish it from other intersex disorders, thus the diagnosis is made by the histological findings. Existence of Leydig cells is demonstrated by testosterone levels above the female range; however, presence of ovarian tissue cannot be ascertained because of the absence of a reliable functional test. Unless appropriate biopsies are performed or the whole gonad is removed, there is a risk of not diagnosing true hermaphroditism. To find a reliable test that can differentiate patients with true hermaphroditism from those with other intersex disorders, we investigated the estradiol (E2) response to human menopausal gonadotropins (hMG) in infants with genital ambiguity. These results were correlated with the histological findings. Eleven infants with genital ambiguity and four with a high scrotal testis were stimulated every 12 h with 2 IU/kg hMG. If E2 rose above 80 pg/mL (cut-off point), the test was discontinued; if after 7 days E2 remained below 80 pg/mL, the hMG dose was doubled and stimulation extended for 7 additional days. In five patients in whom true hermaphroditism was later histologically demonstrated, E2 rose above 80 pg/mL. In two of them, ovarian tissue was removed and hMG stimulation repeated; no response above our cut-off point was observed during the second test. The maximal E2 response to hMG in the remaining 10 individuals was 43 pg/mL; after laparotomy or gonadal biopsies no ovarian tissue was found. The hMG stimulation test can be considered a reliable and safe dynamic procedure for demonstrating the presence or absence of ovarian tissue in infants with genital ambiguity.

Modulation of serum testosterone and autonomic function through stimulation of the male human vomeronasal organ (VNO) with pregna-4,20-diene-3,6-dione.

In mammals, external chemosensory signals from conspecifics of the opposite sex acting on vomeronasal organ receptors can modulate the release of gonadotropins. There is developmental, anatomical and functional evidence showing that the human vomeronasal organ (VNO) has the characteristics of a chemosensory organ. We have been using naturally occurring human pheromones to serve as models for designing novel synthetic compounds that we call vomeropherins. In previous publications we reported that vomeropherin pregna-4,20-diene-3,6-dione (PDD) delivered to the VNO of normal female and male human volunteers significantly affected male subjects only, decreasing respiration and cardiac frequency, augmenting alpha brain waves, and significantly decreasing serum luteinizing hormone (LH) and follicle stimulating hormone (FSH). Results of the present work confirm that PDD produces a local dose-dependent effect in the male human VNO. This is followed by a mild parasympathomimetic effect characterized by 10% increase of vagal tone, together with decreased frequency of electrodermal activity events. Furthermore, PDD locally delivered to the male human VNO significantly decreases serum LH and testosterone (p < 0.01). The present results contribute additional evidence supporting the functionality of the human VNO and its repercussions in autonomic and psychophysiological functions, as well as in neuroendocrine secretions.

Papillary-cystic neoplasm of the pancreas. A sex-steroid dependent tumor.

CONCLUSION: The rate of growth of a papillary-cystic tumor of the pancreas seemed to be enhanced by the concurrence of pregnancy. Progesterone receptors in the tumor were demonstrated by immunohistochemistry and by molecular biology methods. BACKGROUND: Papillary cystic tumor of the pancreas is extremely rare, occurring predominantly young females. Owing to the low frequency of the tumor, there is scarce information about the conditions that promote tumor growth. METHODS: In this report, we present the temporal association between very rapid growth of a papillary-cystic neoplasm and pregnancy. Clinicopathological, immunohistochemical, and molecular biology analyses were performed. RESULTS: A 21-yr-old woman was admitted because of recurrent epigastric abdominal pain associated with episodes of nausea and vomiting, and a history of an abdominal tumor of about 50 mm near the head of the pancreas, detected by ultrasound. On admission the patient had a flat, nontender abdomen without palpable masses. Laboratory analysis including hematologic and hepatic tests were strictly normal; only CA 19-9 (42 U/mL, normal 37 U/mL) was above normal values. One week after admission, an abdominal computerized axial tomography (CAT) scan revealed an 81.6-mm cystic mass localized in the head of the pancreas, and 1 wk later, in a laparotomy, a papillary-cystic neoplasm of 120 mm, limited to the head of the pancreas, was found. Three months later, in a routine follow-up visit, an 18-wk pregnancy was clinically diagnosed and confirmed by ultrasound exploration. The pregnancy continued without complications, and a normal male infant (3.7 kg) was born at 39 wk of gestation, by vaginal delivery. Eighteen months after tumor resection, the patient was asymptomatic and her child was in good health. We propose that progesterone affects tumor growth.

The functionality of the human vomeronasal organ (VNO): evidence for steroid receptors.

The human vomeronasal organ (VNO) is an anatomical entity which is generally considered to be vestigial or non-functional. Nevertheless, a steroidal vomeropherin applied to the human VNO, results in changes of autonomic function, pulsatile release of luteinizing and follicle-stimulating hormones, autonomic and electroencepholographic activity. The vomeropherin pregna-4,20-diene-3,6-dione (PDD) was delivered as pulses in an air stream directed into the lumen of the VNO or to the surface of the olfactory epithelium and respiratory epithelium of the nasal septum. Single stimuli at a concentration of 10(-10) to 10(-8) M produced dose-dependent changes of the electrovomerogram. No significant effects were observed when the same applicator delivered identical stimuli to the nasal respiratory epithelium or to the olfactory epithelium. Administration of the vomeropherin to male subjects changed gonadotropin pulsatility. In males, PDD (5 x 10(9) M) decreased luteinizing hormone (LH) pulsatility which resulted in a statistically significant reduction of plasma LH levels (P < 0.009) and follicle-stimulating hormone (FSH) pulsatility (P < 0.021), but it produced no significant effects in female subjects. Prolactin (PRL) was not significantly affected by this vomeropherin in either male or female subjects. These data demonstrate, for the first time, the existence of a functional vomeronasal-pituitary pathway in adult humans. In addition to the effect on gonadotropin pulsatility, the vomeropherin also produces concurrent reflex autonomic effects after VNO stimulation. These included decreased respiratory frequency, increased cardiac frequency, and event-related changes of electrodermal activity and EEG pattern. Therefore, this investigation also provides evidence for functional connections between the VNO and a variety of hypothalamic areas in adult humans.

Androgen receptor in the rat pancreas: genetic expression and steroid regulation.

Androgens influence the incidence and prevalence of pancreatic cancer in humans and animal models. To our knowledge there has been molecular demonstration of the presence of neither the androgen receptor (AR) nor transcripts of the AR gene. Reverse-transcription polymerase chain reaction (RT-PCR)-Southern blotting was employed for molecular detection and measurement of the androgen receptor messenger ribonucleic acid (AR mRNA) in pancreas. Total RNA obtained from pancreas, prostate, seminal vesicles, and testes of neonatal and adult male and female rats, as well as castrated males substituted with testosterone cyclopentylate, was analyzed by Northern blot technique. Positive hybridization to AR cDNA was obtained in all tissues assayed but not in the pancreas. However, a clear AR 32P cDNA hybridization signal was obtained in pancreatic tissues after cDNA synthesis using RT-PCR-Southern blotting. The levels of the AR transcripts obtained by RT-PCR in the various pancreatic samples were as follows: adult females and neonatal animals > castrated adult males > adult males > castrated adult males substituted with testosterone. These results indicated that the pancreatic tissue possessed transcriptional activity of the AR gene, although to a lesser extent than the typical androgen responsive tissues (prostate and seminal vesicles). In conclusion, transcriptional activity of the AR gene in the pancreas seemed to be modulated by the androgenic milieu in the tissue similar to that reported for the classical androgen-responsive organs.

Maternal behavior in New Zealand white rabbits: quantification of somatic events, motor patterns, and steroid plasma levels.

Several parameters associated with maternal behavior were quantified under laboratory conditions in New Zealand white rabbits. Digging behavior appeared earliest (8-6 days prepartum), its decline preceding the onset of straw carrying (3-1 days prepartum). Hair pulling consummated the construction of the maternal nest. Food intake significantly decreased on days 2 and 1 prepartum. On parturition day, all females spent 300-500 s with the litter while, for the rest of lactation, nursing bouts lasted 199 +/- 7 s. Milk yield increased linearly up to lactation day 19, declining thereafter. Pup weight increased linearly throughout lactation despite the decline in milk yield. Plasma estradiol (E) levels did not significantly vary across pregnancy: 60 +/- 2 pg/ml (days 10-25) and 75 +/- 6 pg/ml (day 30). The testosterone (T) levels at these times were: 200 +/- 10 and 308 +/- 0.03 pg/ml, respectively. Testosterone significantly declined from pregnancy day 30 to lactation day 1 (202 +/- 0.02 pg/ml). Progesterone (P) levels significantly declined from pregnancy day 20 (9 +/- 1 ng/ml) onwards. Progesterone levels were negligible across lactation. Thus, mother rabbits display a sequence of motor patterns and somatic events correlated with changes in plasma levels of T and P against a background of E.

Cellular and humoral immune parameters in women with pathological hyperprolactinemia before and during treatment with bromocriptine.

PROBLEM: Experimental and clinical evidence has suggested an immunostimulatory effect of prolactin and that bromocriptine, an inhibitor of prolactin release, counteracts the actions of prolactin on the immune system. The aim of this study was to determine the impact of elevated serum prolactin levels on the immune system in patients with pathological hyperprolactinemia. METHOD: For this purpose, parameters of the cellular and humoral immune system were studied in six women with prolactinomas and one with idiopathic hyperprolactinemia. Studies were performed when serum prolactin concentrations were high as well as during different phases of the menstrual cycle when prolactin levels had been normalized through treatment with bromocriptine. RESULTS: Hyperprolactinemic subjects, when compared with six age-matched normal women, had significantly higher percentages of total lymphocytes and CD2+ cells. Elevation of CD4+ cells was also observed although to a lesser extent. Bromocriptine-treated patients, when compared with normal women were characterized by increased numbers of total lymphocytes and CD4+ cells, decreased percentage of CD8+ cells, and increased concentrations of serum IgM. These last two findings were also significantly different when compared to those observed in hyperprolactinemia. CONCLUSION: In this study we have described the changes on cellular and immune parameters in patients with hyperprolactinemia before and during bromocriptine therapy, which support the links of communications between the immune and endocrine systems in humans.

Peripheral blood lymphocyte subsets and serum immunoglobulins in Sheehan's syndrome and in normal women during the menstrual cycle.

OBJECTIVE: There has been increasing evidence on the mechanisms underlying the interactions between the neuroendocrine and the immune systems, particularly in animal models with relatively few information in the human. In this study, we evaluate the cellular and humoral immunity in female patients with hypopituitarism and in normal women throughout the menstrual cycle in an attempt to determine the role of pituitary and gonadal hormones on the immune system. DESIGN: Serum immunoglobulins, peripheral blood lymphocyte subsets, and serum hormones were measured in eight patients with postpartum pituitary necrosis (Sheehan's syndrome) and in six normal women along different phases of the menstrual cycle, taking advantage of the lack of pituitary function and the cyclic variations in serum hormones, respectively. RESULTS: Patients with Sheehan's syndrome had higher T lymphocytes (CD2), including helper (CD4) and suppressor (CD8) cell subpopulations and B lymphocytes (CD19) when compared with normal menstruating women. An increase of serum IgA concentrations was also observed. Normal women showed little non-statistically different changes along the menstrual cycle in peripheral blood cell parameters and in serum immunoglobulin levels. CONCLUSIONS: a) Hypopituitarism in humans, in contrast with the animal model, may associate with immune up-regulation at both cellular and humoral levels; and b) hormonal changes along the normal menstrual cycle probably do not influence in great extent the immune system.

Hormonal regulation of the secretory IgA (sIgA) system: estradiol- and progesterone-induced changes in sIgA in parotid saliva along the menstrual cycle.

The effect of estradiol (E2) and progesterone (P4) on the IgA system, both at the systemic and at the mucosal level, was studied in 10 healthy young adult Mexican women during two consecutive menstrual cycles (MC); the control group consisted of five young adult Mexican men. Eight matched samples of blood and parotid saliva were obtained, in which serum E2, P4, and IgA were quantified. Parotid saliva was obtained with Curby's device and sIgA was quantified by an ELISA method. The MC was divided into follicular phase (FP, days 1 to 16) and luteal phase (LP, days 17 to 30). Serum IgA showed slight fluctuations along the period of study, but they were not different between women and men. Irrespective of the phase of the MC, salivary sIgA was higher in women than in men (P < 0.01); sIgA was slightly but not significantly higher in the FP, as compared to the LP. The comparison of phases in each individual woman showed significantly higher levels in the FP (P < 0.01). The profile of sIgA in saliva observed in women resembled the pattern of serum E2 (r = 0.859, P < 0.05), suggesting a possible relation of E2 in the secretion of sIgA by the parotid gland.

Biological characterization of the isoforms of urinary human follicle-stimulating hormone contained in a purified commercial preparation.

The main physicochemical and biological properties of the several isoforms of urinary follicle-stimulating hormone (uFSH) present in a commercially available uFSH preparation were analysed. Purified urinary FSH was submitted to chromatofocusing and several immunoactive forms of uFSH with isoelectric points (pI) ranging from 5.5 to 3.8 were identified. An additional isoform was detected after passing through the chromatofocusing column a 1.0 M NaCl solution (salt peak). Each uFSH isoform or pool of neighbouring isoforms (pI value 5.5-5.1, pool I, 3.8 +/- 1.0% of total immunoactivity recovered; pI value 5.0-4.6, pool II, 18.4 +/- 3.6% of total; pI value 4.5-4.3, pool III, 14.9 +/- 1.5% of total; pI value 4.1, pool IV, 8.2 +/- 1.4% of total; salt peak, pool V, 51.1 +/- 6.4% of total) eluted as single FSH peaks after Sephadex G-100 exclusion chromatography (apparent M(r) 60,000). Even though FSH present within each pool was recognized by a receptor preparation, the receptor binding activity expressed as the radioreceptor assay/radioimmunoassay (RRA/RIA) activity ratio varied with the pI value of the particular uFSH isoform tested; starting from a pI value of 5.5, the receptor binding activity of FSH decreased from 5.9 +/- 0.39 to 2.4 +/- 0.19, as the pI value of the corresponding isoform declined. A similar trend was observed when the potency of each isoform was assessed by an in-vitro bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological characterization of the naturally occurring analogues of intrapituitary human follicle-stimulating hormone.

In the present studies we analysed the main physicochemical and biological properties of the several isoforms of human pituitary follicle-stimulating hormone (hFSH). Extracts of total anterior pituitary glycoproteins from adult donors were submitted to chromatofocusing and several forms of immunoactive hFSH with isoelectric points (pI) ranging from 7.6 to 3.8 were identified. An additional isoform was detected after passing through the chromatofocusing column a 1.0 M NaCl solution (salt peak). Each hFSH isoform or pool of neighbouring isoforms (pI value 7.6-7.1, pool I, 1.5 +/- 0.13% of total immunoactivity recovered; pI value 5.9-5.3, pool II, 8.9 +/- 1.6% of total; pI value 5.0-4.7, pool III, 14.4 +/- 1.4% of total; pI value 4.5-4.1, pool IV, 54.8 +/- 4.9% of total; pI value 3.9-3.8, pool V, 3.67 +/- 0.9% of total; salt peak, pool VI, 16.8 +/- 4.8% of total) eluted as single hFSH peaks after Sephadex G-100 exclusion chromatography (apparent Mr 60,000). Even though hFSH present within each pool was recognized by a receptor preparation, the receptor-binding activity expressed as the radioreceptor assay:radioimmunoassay (RRA/RIA) activity ratio varied with the pI value of the particular hFSH isoform tested; starting from a pI value of 5.9, the receptor-binding activity of hFSH decreased from 4.25 +/- 0.28 to 1.17 +/- 0.14, as the pI value of the corresponding isoform declined. A similar trend was observed when the potency of each isoform was assessed by an in vitro bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum testosterone:dihydrotestosterone ratio and CA 19-9 in the diagnosis of pancreatic cancer.

The testosterone:dihydrotestosterone ratio (T:DHT) and the antigenic marker CA 19-9 were studied in the serum of 21 male patients with pancreatic cancer and 62 controls with other gastrointestinal malignancies or benign pancreatobiliary disease. Specificity of the T:DHT ratio was 98%, significantly better than the specificity of CA 19-9 at both a 37 U/ml cutoff level (61%) and at 100 U/ml (79%). Sensitivity of the T:DHT ratio was 67%, and that of CA 19-9, 71% and 90% at the upper and lower cutoff levels, respectively. False-negative results of the T:DHT ratio were found predominantly in cases of advanced pancreatic cancer, whereas all four stage I patients had an abnormal (less than 5) T:DHT ratio. These results suggest that the T:DHT ratio is a useful marker for pancreatic cancer in males. It can be used alone or in combination with CA 19-9, and should be further evaluated in the differential diagnosis of patients with the early stages of this disease.