Hormonal changes related to eating behavior in oligomenorrheic women.

The aim of this study was to determine those hormonal alterations in the gonadotropin-ovarian axis that are related to eating behavior in oligomenorrheic patients. We studied 74 oligomenorrheic women aged 26.2 +/- 0.8 years, divided into group IA (N = 13) with eating disorders, group IB (N = 61) without eating disorders and 18 normally cycling controls aged 29.2 +/- 1.6 years (group II). No subject had ovarian failure, pituitary disease, thyroid dysfunction or was taking any drug. Blood samples were taken on days 3-6 after the last menses. Luteinizing hormone (LH) was measured in two plasma pools, each made up of three samples taken at 30-min intervals, starting at 15.00 h (LH-15h) and 09.00 h (LH-9h), which allowed the mean LH (mLH) and variability in LH (V-LH: percentage increase from the lower to the higher of the two LH values) to be calculated. Follicle-stimulating hormone (FSH), sex steroids, and gonadotropin-releasing hormone-stimulated LH (sLH) and -FSH (sFSH) were also evaluated. Eating behavior was evaluated with the EAT questionnaire; the EAT 26 score, the dieting score (DS) and bulimia score (BS) were calculated. Dietary intake was evaluated in 35 group IB patients based on food diaries analyzed with the REGAL program, to evaluate daily calorie intake (Cal) and calories provided by carbohydrates (Carb), lipids (Lip) and proteins (Prot). Comparisons between groups were done by analysis of variance (followed by the Fisher PLSD test) and the Kruskal-Wallis test. Groups IA, IB and II did not differ regarding age, body mass index, LH-9h, LH-15h, mLH, FSH, sLH, sFSH, estradiol or dehydroepiandrosterone sulfate; group IA had a higher V-LH than group II (p < 0.02) and a higher testosterone level than groups IB and II (p < 0.05). Positive correlations were found between V-LH and DS (p < 0.01) and BS (p < 0.05), and between testosterone and BS (p < 0.02) and DS (p < 0.05). The V-LH was negatively correlated with Cal and Carb, and testosterone was positively correlated with Cal and Lip. In patients referred for oligomenorrhea, it is concluded that testosterone levels and variability of LH levels are related to eating behavior.

Treatment with long acting repeatable bromocriptine (Parlodel-LAR*) in patients with macroprolactinomas: long-term study in 29 patients.

The aim of the study was to evaluate the short term and long-term effects of long acting repeatable bromocriptine (= Parlodel-LAR*) in patients with macroprolactinomas. Twenty-nine patients (15 men and 14 women) aged 42 +/- 2.7 (M +/- SEM) years were injected with Parlodel-LAR* every 4 weeks during 3.3 +/- 0.3 years. The starting dose was 50 mg/injection, then it was increased to 100 mg in 11 patients and 150 mg in 9 patients. PRL levels decreased in all but one patient 4 weeks after the first injection (270 +/- 59 vs 934 +/- 210 ng/ml, p < 0.001), then became less than 20 ng/ml in 20/29 (69%) patients and finally became undetectable or low in 13/29 (45%) patients. Visual field defects were present in 12/29 patients before treatment. In 11/12 patients, treatment with Parlodel-LAR* resulted in an improvement and complete correction of visual field defects was observed in 8/12 patients. Adenoma size (2.5 +/- 0.2 cm before treatment) was reduced by at least 20% in 24/29 (83%) patients. Disappearance of adenoma was observed on CT scan in 8/29 (28%) patients after 28.7 +/- 5.3 months of treatment. Minor side effects occurred in 20 patients after the first injection then disappeared in 18 patients within the following 6 months of treatment. One patient had rhinorrhea after 3 months of treatment. Treatment with Parlodel-LAR* results in beneficial short-term effects (with rapid correction of recent onset visual field defects) and long-term effects (which can include complete disappearance of adenoma on CT scan evaluation) in patients with macroprolactinomas.

Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans.

Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) levels were evaluated in euthyroid (N = 111), hyper- (N = 58) and hypothyroid (N = 38) men, in pre- and postmenopausal women (study 1) and in hyper- (N = 24) and hypothyroid (N = 15) patients before and after treatment with carbimazole or levothyroxine therapy (study 2). The SHBG levels are increased in hyper- and decreased in hypothyroid patients, whereas CBG levels are increased in hypo- and decreased in hyperthyroid patients. The SHBG levels are higher in women than in men with similar thyroid status. Plasma SHBG levels are correlated positively whereas CBG levels are correlated negatively with free thyroid hormone concentrations in men as well as women. In hypothyroid patients, SHBG concentrations increased (p < 0.01) and CBG concentrations decreased (p < 0.01) during levothyroxine treatment. In hyperthyroid patients, SHBG concentrations decreased (p < 0.01) and CBG concentrations increased (p < 0.01) during antithyroid treatment. The SHBG and CBG concentrations in treated hypo- and hyperthyroid patients were not significantly different from those of euthyroid controls. Our data indicate that SHBG and CBG levels depend on thyroid status. Corticosteroid-binding globulin is an index of thyroid hormone action at the liver level whose changes are opposite to those of SHBG in hyper- and hypothyroidism.

Increased biological activity due to basic isoforms in recombinant human follicle-stimulating hormone produced in a human cell line.

FSH has four asparagine-linked oligosaccharides with variable sialic acid contents, so that FSH is not a single molecule, but a heterogeneous group of isoforms. These isoforms differ in their biological properties and their distribution changes in various physiological states, allowing the modulation of FSH activity. Recombinant human (h) FSH has been produced in Chinese hamster ovary cells and has an isoform profile similar to those of both pituitary FSH standard and purified urinary FSH. These FSH preparations, however, do not contain the full spectrum of FSH isoforms found in the circulation. Production of recombinant hFSH in a cell line with a different pattern of glycosylation could broaden its isoform profile and potentially alter its biological activity. Thus, we transfected human embryonal kidney cells (293) with the human alpha and FSH beta genes to produce recombinant hFSH (hFSH-293) and determined its biological activity in a rat granulosa cell bioassay. Although hFSH-293 was immunologically indistinguishable from pituitary FSH standard, its biological potency was 3- to 6-fold higher than those of two different pituitary FSH standards. To investigate this increased potency, we separated the isoforms of hFSH-293 by chromatofocusing and determined their biological potencies in the rat granulosa cell bioassay. The isoform profile of hFSH-293 demonstrated a greater number of basic isoforms than that of pituitary FSH standard. Several of these basic isoforms exhibited enhanced in vitro biological potency, accounting for the increased biological potency of hFSH-293. This pattern of high in vitro biological activity and more basic isoforms is analogous to the FSH circulating during GnRH stimulation, pubertal induction, and ovulation.

Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis.

We studied the luteinizing hormone (LH) secretory pattern in three patients, aged 30, 23 and 43 years, with gynecomastia due to Leydig cell tumor of the testis, before and 6 months after unilateral orchidectomy. The results were compared to those of 11 normal fertile controls aged 20-35 years. Blood sampling was done at 20-min intervals from 22.00 h to 10.00 h. The LH data were analyzed with the Cluster analysis algorithm with "optimal parameters for LH male data" to determine the pulse interval and pulse amplitude. The Expfit program was applied to LH pulses to calculate the apparent half-life of immunoreactive LH. Before surgery, when compared to controls, the patients had a low to normal testosterone/estradiol ratio (0.053, 0.110, 0.046 vs 0.148 +/- 0.038) and mean LH levels (1.96, 3.7, 2.55 vs 4.0 +/- 1.9 IU/l), decreased pulse amplitude (2.65, 3.01, 2.21 vs 3.31 +/- 1.41 IU/l) and reduced apparent half-life of LH (74, 69, 78 vs 97 +/- 16 min). After removal of the Leydig cell tumor, the testosterone/estradiol ratio returned to the normal range (0.141, 0.177, 0.093) while an increase in mean LH levels (5.75, 7.90, 4.88 IU/l), LH pulse amplitude (3.07, 6.05, 2.86 IU/l) and apparent half-life of LH (138, 106, 104 min) was observed in all three patients. Our data indicate that endogenous hyperestrogenism in patients with Leydig cell tumor of the testis results in an inhibition of LH secretion, and suggests that such inhibition could result from a reduction in pulse amplitude and apparent half-life.

Site-directed mutagenesis defines the individual roles of the glycosylation sites on follicle-stimulating hormone.

To determine the specific role of each follicle-stimulating hormone (FSH) oligosaccharide, we mutated Asn to Gln at each glycosylation site (alpha Gln52, alpha Gln78, alpha Gln52-78, beta Gln7, beta Gln24, and beta Gln7-24) to selectively inhibit oligosaccharide attachment. For wild-type and mutant FSH, we determined the binding affinity to homogenized rat Sertoli cells and the signal-transducing activity in cultured rat granulosa cells. The binding affinity of FSH lacking any one of the oligosaccharides was increased over wild-type FSH, while the signal-transducing activity of FSH lacking the oligosaccharide at alpha Asn52 (alpha Gln52 FSH) was markedly reduced, and that of FSH lacking either beta oligosaccharide (beta Gln7 and beta Gln24 FSH) was slightly reduced. At each FSH beta glycosylation site, we made a second amino acid substitution to inhibit glycosylation (beta Tyr9 and beta Tyr26) and an amino acid substitution that preserved glycosylation (beta Ser9 and beta Ser26). The amino acid sequence of the second beta subunit glycosylation site was important for signal transduction, regardless of the presence or absence of the oligosaccharide. Thus, while each FSH oligosaccharide has a similar impact on binding affinity, the alpha 52 oligosaccharide has a disproportionate role in signal transduction, and the amino acid sequence at beta Asn24 functions in both binding and signal transduction.