Le traitement du carcinome différencié de la thyroïde est chirurgical. Il est souvent complété par l’administration d’iode radioactif. À ce jour, les conséquences de ce traitement sur la fonction testiculaire sont mal connues.

L’acromégalie est associée à des comorbidités cardiovasculaires, respiratoires et métaboliques. L’effet du pegvisomant, un antagoniste du récepteur de la GH, sur la baisse de l’IGF-1 est bien documenté, contrairement à son effet sur les comorbidités. Le but de cette étude rétrospective monocentrique était d’évaluer l’effet à long terme du pegvisomant sur le retentissement cardiovasculaire, pulmonaire et métabolique de l’acromégalie. Nous avons analysé l’effet du pegvisomant (jusqu’à 10 ans), donné seul (n = 19) ou associé aux autres traitements, sur les paramètres de l’échographie cardiaque, de la polysomnographie et métaboliques chez 42, 12 et 26 patients, respectivement. Nous montrons qu’après 20 ± 16 mois de traitement par pegvisomant, l’IGF-1 est normalisée chez 29 patients (69 %). La fraction d’éjection (FEVG) est améliorée chez les patients ayant une FEVG initialement < 60 % et diminuée chez ceux ayant une FEVG > 70 %. La masse ventriculaire gauche (MVG) est diminuée chez les 17 patients ayant une MVG supérieure à la médiane de 91 g/m2 (123 ± 25 à 101 ± 21 g/m2 [p < 0,05]), la MVG restant stable chez les autres patients. Le suivi à long terme de 22 patients montre que ces modifications persistent dans le temps. Le pegvisomant permet d’améliorer l’index apnée-hypopnée et de faire disparaître le syndrome d’apnée du sommeil chez 4 patients. Enfin, le pegvisomant s’accompagne d’une élévation de l’index de masse corporelle et du LDL-cholestérol sans modification des autres paramètres lipidiques et de la glycémie. Ainsi, le pegvisomant permet non seulement de normaliser l’IGF-1 mais aussi d’améliorer les comorbidités associées à l’acromégalie.

Déterminer les mécanismes physiopathogéniques liés à l'hypotestostéronémie d'exercice et leur finalité.La testostérone, principale hormone anabolisante de l'homme, exerce de nombreux effets sur la physiologie organique, par le biais d'un récepteur unique et spécifique. Son action est double: androgénique et anabolique, et au cours de l'exercice, elle s'oppose aux effets cataboliques du cortisol. Les taux circulants de testostérone évoluent dans deux sens différents durant les efforts physiques. Une élévation de la concentration plasmatique est toujours enregistrée au début de l'exercice, suivie d'une baisse en deçà du niveau basal normal quand l'effort se prolonge. Cette adaptation endocrinienne représente une régulation indispensable au niveau musculaire. Elle permet à l'organisme de poursuivre l'exercice physique, en favorisant la glycogénolyse, et en facilitant la mise en place des processus de la gluconéogenèse. Par ailleurs, l'étude des récepteurs à la testostérone par le biais de techniques de radio-compétition permet de confirmer qu'en fonction des taux circulants de testostérone, l'expression de l'affinité hormonale est plus importante quand le taux de testostérone est faible, comme c'est le cas au cours des efforts de longue durée. Cette expression sera en revanche altérée en cas d'élévation de la testostéronémie.Ces résultats confirment en conséquence l'inutilité d'un quelconque apport exogène d'anabolisants, relevant alors du dopage.To define the physiopathogenic mechanisms of hypotestosteronemia concerning exercice, and their adaptation.Testosterone, the principal anabolic-androgenic steroid hormone in man, exercises numerous effects on physiological metabolism through a specific and unique receptor. It has a double action: anabolic and androgenic, and it counteracts the catabolic effect induced by cortisol during physical exercise. Circulating testosterone levels evolve in two different ways during physical exertion. There is always an increase at the beginning of the exercise, followed by a below-normal level during the course of exercise. This endocrinic adaptation represents an essential regulation in the muscle. It allows the pursuit of physical exercise, promoting glycogenolysis and facilitating the process of gluconeogenesis. Moreover, a study on testosterone receptors using techniques based on the radio-competition principles confirms that, as a function of circulating testosterone levels, the hormonal affinity expression is more significant when testosteronemia is low, as in, for instance, prolonged exercise. This hormonal expression deteriorates when testosteronemia is elevated.These results corroborate the uselessness of any exogenous anabolic contribution, as is the case during doping.

La baisse de la DHEA avec l’âge, corrélée avec des anomalies liées au vieillissement, est un argument pour envisager son administration. Des doses permettant de retrouver des concentrations sériques de sDHEA comparables à celles des adultes jeunes sont bien tolérées sur des périodes courtes (six mois à un an) et semblent avoir un effet positif bien que modeste sur l’os des femmes âgées et ce, de manière d’autant plus importante que la concentration sérique de sDHEA avant traitement est basse. La DHEA semble agir en diminuant la résorption tout en stimulant la formation osseuse. Ces effets sont probablement liés principalement à la conversion de la DHEA en stéroïdes sexuels actifs, estradiol et testostérone, ce qui explique l’absence d’effet retrouvé chez l’homme (qui même très âgé conserve une imprégnation androgénique d’origine testiculaire) mais d’autres mécanismes d’action, comme l’augmentation de l’IGF-I, ne sont pas à exclure. Le positionnement de la DHEA comme thérapeutique anti-ostéoporotique est bien entendu largement prématuré du fait de l’absence d’études sur une éventuelle épargne fracturaire et de la méconnaissance de possibles effets néfastes à long terme.As the serum concentrations of dehydroepiandrosterone (DHEA) and its sulfate ester (sDHEA) decrease dramatically with age in parallel with the appearance of some clinical symptoms of aging, it has been proposed to test the benefits of DHEA supplementation in the elderly. Daily oral doses of DHEA allowing to reach serum concentrations of sDHEA in the young adults range are well tolerated over short periods (6 months to one year) and seem to have beneficial, although modest, effects on bone health of elderly women, particularly in those with low serum sDHEA before treatment. DHEA appears to act by decreasing bone resorption, while stimulating or at least maintaining bone formation. These effects are likely to be due to the conversion of DHEA into active steroids, estradiol and testosterone, rising a plausible explanation to the lack of effect observed in men who, even very old, maintain an androgen secretion to testicular origin. However, other mechanisms such as an increase in IGF I, should not be excluded to explain the bone-sparing effects of DHEA. Despite its potential positive effects on bone, considering DHEA as an anti-osteoporotic therapy would be greatly premature because of a lack of study on the reduction in fracture occurrence, and a lack of knowledge on possible long-term side-effects.

In this paper, we present our Semantic Web system for the storage of 19,448 agricultural alert bulletins in France. The archive of alert bulletins was published on the Web as Linked Open Data (LOD). LOD uses Semantic Web technologies to publish data on the Web. Some best practices for publishing Linked Data are already proposed. We enrich these best practices in order to meet some specific information retrieval needs: spatiotemporal and thematic annotations and aggregation indicators. We illustrate our proposal by the publication of our archive. We describe our methodology for building the system and highlight the interest regarding Semantic Web technologies for this agricultural alert storage, publication and analysis. To prove that our system answers our needs, we propose some queries to illustrate the calculation of spatiotemporal aggregation indicators.

Medical treatment of hyperprolactinemia is based upon use of dopamine agonists (DA): bromocriptine, lisuride, quinagolide and cabergoline. In over 80% of cases, these drugs induce normal prolactinemia and ovulatory cycles. In resistant cases, the DA should be changed. Tolerance may occasionally be poor, particularly with bromocriptine, which appears less well-tolerated than quinagolide and than cabergoline above all. In the event of intolerance to a given DA, another should be tried. In patients with macroprolactinoma treated with DA, MRI monitoring should be carried out after 3 months of treatment to verify tumor size reduction, then after 1 year, yearly for the next 5 years and once every 5 years if adenoma size is stable. In cases of microprolactinoma, control under treatment is pointless. MRI may be performed after 1 year and then after 5 years. Once normal prolactin levels have been achieved, attempts may be made to stop the treatment. When a prolonged treatment is interrupted, especially with cabergoline, progressive increase in serum prolactin and return of hyperprolactinemia symptoms are seen in only around 20 to 30% of cases, particularly when residual adenoma exists after prolonged treatment. Nevertheless, prolactin levels should continue to be monitored after discontinuation of DA, possibly with MRI monitoring, since prolactin levels may rise again after a number of months or years. When normal prolactin levels have been achieved with DA, another solution consists in reducing the dose or dosing frequency of DA in steps to the lowest effective dose consistent with maintenance of normal prolactin levels and stable adenoma size. For drug-induced hyperprolactinemia, where the causative medication cannot be withdrawn, it is often pointless and possibly even dangerous to administer a DA. It is therefore necessary to check for absence of pituitary adenoma and where necessary, begin treatment with sex steroids so as to ensure satisfactory impregnation with sex steroids and avoid osteoporosis. For macroprolactinoma, the first-line treatment is drug therapy with DA. At present, there is no evidence to suggest that prior treatment with DA can modify the outcome of surgery. With microprolactinoma, DA treatment offers a good first-line therapeutic option but surgery may also be useful. DAs for microprolactinoma may be withdrawn after menopause.Le traitement médical de l'hyperprolactinémie fait appel aux agonistes dopaminergiques (DA) : bromocriptine, lisuride, quinagolide, cabergoline. Dans plus de 80 % des cas, une prolactinémie normale et des cycles ovulatoires sont obtenus sous DA. En cas de résistance, il faut changer de DA. La tolérance est parfois médiocre, en particulier avec la bromocriptine qui semble moins bien tolérée que le quinagolide et surtout la cabergoline. En cas d'intolérance à un DA, il ne faut pas hésiter à changer d'agoniste. Sous DA, en cas de macroprolactinome, la surveillance IRM sera faite après trois mois de traitement pour vérifier la diminution tumorale puis après un an, puis tous les ans pendant cinq ans et une fois tous les cinq ans lorsque le volume de l'adénome est stable. En cas de microprolactinome, un contrôle est inutile sous traitement. Une IRM peut être faite après un an puis cinq ans. Une fois la normalisation de la prolactine obtenue, on peut essayer d'arrêter le traitement. En effet, lorsque le traitement, en particulier par cabergoline, a été prolongé, la réascension de la prolactinémie et le retour des symptômes de l'hyperprolactinémie ne sont observés que dans 20 à 30 % des cas environ, surtout s'il existe un résidu adénomateux après traitement prolongé. Il faudra néanmoins poursuivre la surveillance de la prolactinémie, voire de l'IRM, après l'arrêt du DA car il faut parfois plusieurs mois ou années pour que la prolactinémie remonte. Une autre solution consiste, lorsqu'une prolactinémie normale a été obtenue sous DA, de diminuer par paliers la posologie du DA ou sa fréquence d'administration jusqu'à la moindre dose efficace permettant le maintien d'une prolactinémie normale et d'un volume adénomateux stable. En cas d'hyperprolactinémie médicamenteuse, s'il est impossible d'interrompre le médicament responsable, il est souvent inutile, voire dangereux de donner un DA. Il faut donc vérifier l'absence d'adénome hypophysaire et, si nécessaire, donner un traitement par stéroïde sexuel de façon à assurer une imprégnation en stéroïde sexuel satisfaisante et éviter une ostéoporose. En cas de macroprolactinome, le traitement de première intention est le traitement médicamenteux par les DA. Actuellement, il n'existe pas d'argument pour penser qu'un traitement préalable par les DA avant la chirurgie modifie les résultats du geste chirurgical. En cas de microprolactinome, le traitement médicamenteux par les DA constitue une bonne option thérapeutique en première intention, mais la chirurgie est aussi possible On peut interrompre le traitement DA après la ménopause en cas de microprolactinome.

Serum anti-Mullerian hormone (AMH), a prepubertal Sertoli cell marker, declines during puberty as an early sign of testicular testosterone (T) production. When T synthesis or action is impaired, serum AMH is abnormally high in the first months after birth and at puberty but normal between these two periods. We postulated that FSH might be responsible for AMH up-regulation in the absence of androgen inhibition. To test this hypothesis, we administered recombinant human (rh) FSH to eight patients aged from 18-31 yr with untreated congenital hypogonadotropic hypogonadism. This situation is ideal to study the effect of FSH on AMH production because it avoids interference by endogenous gonadotropins and T. The patients received daily sc injections of 150 IU rhFSH for 1 month, followed in seven of them by a combined treatment of rhFSH plus human chorionic gonadotropin (hCG; 1500 UI im, twice a week) for 2 months. Gonadotropins, T, AMH, and inhibin B were measured in plasma before treatment every 10 d during rhFSH treatment and every month during combined rhFSH and hCG treatments. All hormones were at prepubertal levels before treatment. Although LH and T did not vary, AMH and inhibin B levels gradually increased after 20 d of FSH administration. However, in contrast to rhFSH alone, the combined rhFSH plus hCG stimulation of the testis dramatically suppresses the secretion of AMH and induced a modest but significant reduction of circulating inhibin B levels. We conclude that FSH stimulates AMH production in the testis when it is at a prepubertal stage. In addition, the decrease of serum AMH during combined rhFSH and hCG testicular stimulation is in agreement with the concept that during pubertal development and in adult life, the suppressive effect of LH-driven testicular androgens outweighs the stimulating effect of FSH on AMH production by Sertoli cells. Finally, the hCG-induced decrease in inhibin B suggests that in humans, as previously demonstrated in monkeys, testicular T is also able to inhibit inhibin B secretion.

It is currently believed that the postmenopausal ovary remains a gonadotropin-driven, androgen-producing gland. However, the adrenal contribution to circulating androgen levels may explain some conflicting results previously reported. In addition, the steroidogenic potential and gonadotropin responsiveness of the postmenopausal ovary have not been recently reassessed. Plasma T, bioavailable T, free T, androstenedione (Adione), and dehydroepiandrosterone sulfate levels were measured in postmenopausal or ovariectomized women with complete adrenal insufficiency, compared with women with intact adrenals. A stimulation human chorionic gonadotropin test (on d 0, 3, and 6) was performed in postmenopausal women with adrenal insufficiency. Dexamethasone was administered for 4 d in postmenopausal women with intact adrenals. Intraovarian T and androstenedione were also measured in homogenates of ovarian tissue from postmenopausal women. Immunocytochemistry was performed on postmenopausal ovaries and premenopausal controls to detect the presence of steroidogenic enzymes (P-450 aromatase, P-450 SCC, 3 beta HSD, and P-450 C17) and gonadotropin receptors. Plasma androgen levels were below or close to the limit of the assay in all women with adrenal insufficiency. They were similar in postmenopausal and oophorectomized women with normal adrenals. No hormonal changes were observed after human chorionic gonadotropin injections in women with adrenal insufficiency. In contrast, a dramatic decrease of all steroids was observed after dexamethasone administration in postmenopausal women with intact adrenals. Intraovarian T and androstenedione levels were negligible in postmenopausal ovarian tissue. P-450 aromatase was absent from the 17 ovaries studied, and the enzymes for androgen biosynthesis were either absent (n = 13) or present in very low amounts (n = 4). In all the postmenopausal ovaries, FSH and LH receptors were completely absent. In the absence of adrenal steroids, postmenopausal women have no circulating androgens. This result is consistent with the immunocytochemical studies showing the almost constantly absent steroidogenic enzymes and LH receptors in the postmenopausal ovary. Thus, the climacteric ovary is not a critical source of androgens. The arrest of androgen secretion after menopause may impact significantly on women's health.

UNLABELLED Experimental data suggest that FSH-stimulated Sertoli cells can enhance LH-induced Leydig cell testosterone (T) production. The function of Leydig and Sertoli cells can be selectively studied by using recombinant human LH (rhLH) and recombinant human FSH (rhFSH) in patients with complete gonadotropin deficiency. The aim of the present study was to assess the secretion of testicular T, estradiol (E2), and inhibin B and the physiological relevance of the Sertoli-Leydig cell interaction in man. For that purpose, six patients with acquired complete hypogonadotropic hypogonadism received the following treatments for three periods of 1 month in a random order: 1) rhLH, 900 IU/day sc; 2) rhFSH, 150 IU/day sc; and 3) combined rhLH/rhFSH treatments. Each treatment period was separated by a washout period of 15 days. Plasma LH, FSH, T, E2, and inhibin B were measured before and every 10 days during each treatment. During rhLH administration, mean plasma LH levels rose significantly from 0.4 +/- 0.2 IU/L to 11.7 +/- 1.2 IU/L (P < 0.01) and plasma FSH levels did not change. rhFSH administration induced a significant increase in plasma FSH levels (from 0.5 +/- 0.4 to 12.1 +/- 1.4 IU/L; P < 0.01), whereas mean plasma LH levels remained low. Mean plasma E2 levels were unchanged during rhFSH treatment, but they increased significantly during rhLH from 22 +/- 4 to 54 +/- 8 pmol/L (P < 0.01) and during rhLH plus rhFSH administration. rhFSH treatment induced a sustained elevation of mean plasma inhibin B levels from 58 +/- 13 to 175 +/- 25 pg/mL (P < 0.01), similar to the increase occurring during rhFSH plus rhLH administration. In contrast, mean plasma inhibin B levels did not increase during rhLH administration. Finally, a similar and significant increase in mean plasma T levels occurred during both rhLH and rhLH plus rhFSH treatment from 0.9 +/- 0.3 to 5.4 +/- 0.7 nmol/L (P < 0.01) and from 1.0 +/- 0.4 to 6.0 +/- 0.9 nmol/L (P < 0.01), respectively. In contrast, during rhFSH treatment mean plasma T levels remained unchanged when compared with baseline. IN CONCLUSION 1) the increase of plasma E2 induced by rhLH and the absence of effect of rhFSH confirm that Leydig cells are the major site of testicular E2 production in man; 2) the secretion of inhibin B is increased by rhFSH and not by rhLH, and, thus, Sertoli cells seem to be the main source of inhibin B production; and 3) the increase of plasma T induced by rhLH is not enhanced by rhFSH. These results suggest that the stimulatory effect of FSH on Leydig cell steroidogenesis by a Sertoli cell paracrine factor does not seem to play a major physiologic role in man.

Little is known about the physiological secretion of the free beta-subunit of LH (LHbeta). The aim of this study was to compare in women the secretion of LHbeta, using sensitive and specific two-site immunoassays, with dimeric LH and the free common alpha-subunit (FAS). The LHbeta assay does not recognize the dimeric LH and cross-reacts only with free hCG beta-subunit (CGbeta). Thus, all of the plasma samples were also tested with a highly specific immunoradiometric assay for free CGbeta. Molar concentrations (i.e. picomoles per L) were used to compare the plasma levels of LH and its free subunits. Plasma LH, LHbeta, FAS, and CGbeta levels were measured in five normally cycling women during the early follicular phase and the ovulatory peak of LH. The pulsatile profiles of LH, LHbeta, FAS, and CGbeta were studied in five postmenopausal women before and 21 days after injection of a depot preparation of the GnRH agonist D-Trp6 (3.75 mg, im) and in five women with functional hypothalamic amenorrhea (FHA), i.e. low plasma LH levels, during pulsatile GnRH administration (20 microg/pulse, 90 min, sc). Afterward, one of the patients with FHA received a single sc injection of 1350 U recombinant human LH, and plasma LH, LHbeta, FAS, and CGbeta levels were measured and compared with the high plasma levels of one postmenopausal woman. In cycling women, basal plasma LHbeta and CGbeta levels were below the detection limit of the assays (1.34 and 0.65 pmol/L, respectively), and plasma FAS levels were 13.60 +/- 0.13 pmol/L. During the LH surge, there was a parallel increase in LH, LHbeta, and FAS. Plasma CGbeta levels remained undetectable. In normal postmenopausal women, basal plasma dimeric LH, LHbeta, and FAS levels were increased in parallel, and their pulsatile profiles were similar, without measurable plasma CGbeta levels. After D-Trp6 administration, plasma LH and LHbeta levels were completely suppressed, whereas plasma FAS levels increased, and plasma CGbeta remained below 0.65 pmol/L. In FHA women, basal plasma levels of LH and FAS were low, without detectable LHbeta and CGbeta levels. During pulsatile GnRH administration, LHbeta became detectable, and pulses were synchronous with those of LH and FAS. The secretion of LH and LHbeta was almost equimolar. Plasma CGbeta levels remained undetectable. In the patient with FHA, administration of recombinant human LH increased only plasma LH levels, whereas plasma LHbeta and FAS levels remained very low. In conclusion, when the production of dimeric LH increases, a concomitant, parallel, and almost equimolar hypersecretion of uncombined and biologically inactive LHbeta occurs. Like the alpha-subunit, LHbeta may be secreted in the dissociated free form. This can lead to pitfalls during clinical investigations if assays of free CGbeta display some cross-reaction with free LHbeta.

We have previously shown in postmenopausal women that a 19-nor-progesterone derivative, nomegestrol acetate (NOMA) had a strong antigonadotropic activity and that this effect was not mediated via the androgen receptor. The aim of the present study was to further assess the action of this progestin on gonadotropin secretion in women. To demonstrate at which level of the hypothalamo-pituitary-ovarian axis the gonadotropin inhibition was exerted, 10 normally cycling (NC) women, 3 women with a gonadotropin-independent ovarian function [McCune-Albright (MCA) syndrome], and 5 women with functional hypothalamic amenorrhea (FHA) participated in the study. NC women were treated orally with 5 mg NOMA for 21 days, after one control cycle. Plasma estradiol (E2) and progesterone, LH, and FSH levels were measured during each cycle. A frequent sampling study (every 10 min for 4 h), followed by a classic GnRH test (100 microg, i.v.), was performed on day 11. Women with MCA were studied before, during NOMA, and after long-acting GnRH agonist administration. In women with FHA, pulsatile GnRH (20 microg s.c., every 90 min) was given for two cycles with or without NOMA (5 mg for 21 days). In all NC women, ovulation was suppressed by NOMA. Mean plasma LH levels, LH pulse frequency, and the LH response to exogenous GnRH were significantly decreased. In MCA, neither NOMA nor GnRH agonist modified multiple ovarian cysts on ultrasound or plasma E2, levels which remained elevated, ruling out a direct ovarian effect. In FHA, pulsatile GnRH administration recreated a normal ovulatory menstrual cycle. Addition of NOMA prevented the increase of plasma E2, decreased the amplitude of LH pulses, and prevented ovulation. In view of this unexpected action of NOMA at the pituitary level, seven samples of normal human female pituitaries were tested for the presence of progesterone receptor (PR) using a double labeling immunocytochemical technique. The presence of PR was detected in the seven human pituitary tissues. In addition, PR was found to be expressed only in gonadotroph cells. In conclusion, NOMA, a 19-nor-P derivative, has a potent antigonadotropic activity exerted at the hypothalamic level, inhibiting ovulation in NC women. In women with FHA, NOMA decreased the gonadotropin stimulation induced by pulsatile GnRH administration. According to the presence of PR in gonadotroph cells of normal human pituitaries, 19-nor-progesterone derivatives may also act on the gonadotropin secretion at the pituitary level.

OBJECTIVEFunctional hypothalamic amenorrhoea (FHA) is a consequence of low dietary intake as observed in two major pathophysiological conditions, anorexia nervosa and/or intensive physical exercise. The aim of the present study was to assess in women with FHA and normal body mass index (BMI) and apparently normal daily activities, the degree of impairment of GnRH secretion, its nutritional origin and its reversibility.PATIENTSTwelve women (22–35 years) with FHA not related with exercise and 12 age and BMI matched menstruating controls (NC) were studied. Six women with congenital hypothalamic hypogonadism (CHH), representative of complete gonadotrophin deficiency, were also enrolled for comparison.DESIGNPlasma oestradiol (E2) and androstenedione (A) levels were measured and the pulsatile profile of LH was studied. A GnRH agonist test, using 100 μg S/C of DTrp6 GnRH (Triptorelin) was performed (sampling every 2 h for 24 h). Dietary intake, body composition and nutritional markers (FT3, ferritin, retinol binding protein (RBP), SHBG, IGF‐I and leptin) were measured. All the women with FHA were advised to normalize their diet during four months. The same studies were performed if nutritional markers and body composition were normalized.RESULTSIn FHA, mean plasma E2 and A levels were low. LH pulse frequency and amplitude were significantly reduced compared to NC (P < 0.005). FSH/LH ratio increased rapidly after triptorelin with a significant increase in plasma E2 levels between 18 and 24 h. In contrast, no response to triptorelin was observed in women with CHH.The fat body mass was lower and the lean body mass higher in FHA than in NC. Marked differences in nutritional intake were identified, with altered dietary composition. FHA consumed significantly less fat (P < 0.001) and less carbohydrate (P = NS) than the BMI‐matched controls. Mean plasma levels of SHBG were increased whereas mean plasma levels of FT3, ferritin, RBP, IGF‐I, and leptin were significantly decreased. Only three patients with FHA kept a balanced diet and improved their body composition after 4 months. LH pulsatile profile and response to triptorelin challenge were normalized in these patients.CONCLUSIONMild dieting, close to normal but prolonged and characterized by an important fat restriction, is able to interfere with gonadotrophin secretion. Assessment of nutritional markers allows recognition of mild nutritional insufficiency as a common cause of FHAs. The gonadotrophin deficiency is partial and may be reversible after improvement of nutritional intake and body composition.

Recent studies have suggested that human choriogonadotropin (hCG), in addition to its function in regulating steroidogenesis, may also play a role as a growth factor. Immunocytochemistry using two different monoclonal antibodies (LHR29 and LHR1055) raised against the human luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor allowed us to detect this receptor in breast cancer cell lines (T47D, MCF7, and ZR75) in individual cancer biopsies and in benign breast lesions. The receptor was also present in epithelial cells of normal human and sow breast. In the latter, its concentration increased after ovulation. The presence of LH/hCG receptor mRNA was confirmed by reverse transcription-PCR using primers extending over exons 2-4, 5-11, and 9-11. The proportion of LH/hCG-receptor positive cells and the intensity of the immunolabeling varied in individual biopsies, but there was no obvious correlation with the histological type of the cancer. These results are compatible with previous studies suggesting that during pregnancy, hCG is involved in the differentiation of breast glandular epithelium and that this hormone may play an inhibitory role in mammary carcinogenesis and in the growth of breast tumors.

The physiological importance and therapeutical interest of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are still controversial. Panhypopituitarism is characterized by the absence of secretion of adrenal and gonadal steroids and thus the production of their metabolites. The conversion of DHEA given orally into delta 5 derivatives, androgens, androgen metabolites, and estrogens was studied in ten patients with complete panhypopituitarism. Sex steroid therapy was withdrawn for at least 2 months. Each patient received, at 1-month intervals and in a random order, two single oral doses of DHEA (50 mg and 200 mg) and placebo. During each treatment, urine samples were collected for 24 h, and blood samples were drawn at hourly intervals for 8 h. In patients with pituitary deficiency, plasma DHEA and DHEAS were not detectable and increased, with the 50 mg dose, up to levels observed in young adults. The administration of 200 mg of DHEA induced an increase of both steroids to supraphysiological plasma levels. A small increase of delta 5-androstenediol was observed. In contrast, the increase of plasma delta 4-androstenedione was important and dose dependent. DHEA was also converted into the potent sex steroid testosterone (T). The administration of a 50 mg dose of DHEA restored plasma T to levels similar to those observed in young women. The 200 mg dose induced an important increase of plasma T, slightly below the levels observed in normal men. The increase of plasma dihydrotestosterone levels was small at both doses of DHEA, in contrast with the large conversion of DHEA into androsterone glucuronide and androstanediol glucuronide. Finally, DHEA administration induced a significant and dose dependent increase of plasma estrogens and particularly of estradiol. In conclusion, this short term study demonstrates that: 1) panhypopituitarism is a model of interest to study the metabolism of DHEA; 2) in the absence of pituitary hormones and of adrenal and gonadal steroids, DHEA given orally is mainly converted into delta 4 derivatives, which in turn are strongly metabolized into 5 alpha-3keto-reduced steroids; 3) a significant increase of sex active hormones was observed in plasma after 200 and even 50 mg of DHEA. Thus, biotransformation of DHEA into potent androgens and estrogens may explain several of the reported beneficial actions of this steroid in aging people.

To further study the mechanism of the antigonadotropic activity of progestins, the effects of a 19-nortestosterone derivative, norethisterone acetate (NETA), and a 19-norprogesterone derivative, nomegestrol acetate (NOMA), were compared. The aim was to assess whether their action is exerted via the androgen receptor. Ten healthy postmenopausal women were treated for five monthly periods of 24 days separated by 10 days in a randomized cross-over design. Transdermal estradiol, Estraderm TTS (25 micrograms; one patch every 3 days), was given from days 1-24 during the five periods. On the last 12 days, of each estradiol treatment, they all received a placebo, NOMA (5 mg/day), NOMA in association with the nonsteroidal antiandrogen, flutamide (FLU; 250 mg, twice a day), NETA (10 mg/day), or NETA plus FLU. On the other hand, three castrated patients with complete androgen insensitivity (CAI) received NOMA and NETA for two periods of 12 days separated by 3 weeks. In postmenopausal women, the effects of NOMA and NETA on metabolic parameters were studied. Only NETA decreased high density lipoprotein cholesterol. Plasma LH, FSH, and estradiol were measured during each treatment period. A significant decrease in mean plasma LH and FSH levels and their responses to exogenous GnRH was observed with NOMA and NETA treatments compared to placebo (P < 0.001). The pulsatile frequency, but not the amplitude, of LH was significantly decreased during both treatments. Interestingly, the effects of both progestins on gonadotropins were not antagonized by FLU administration. In the patients with CAI, the pulsatile study of gonadotropins was performed before and on day 12 of NOMA and NETA treatments. As in postmenopausal women, both progestins induced similar decreases in LH and FSH. In conclusion, a 19-nortestosterone derivative, NETA, and a 19-norprogesterone derivative, NOMA, have similar antigonadotropic activities. This effect, not antagonized by FLU and observed in patients with CAI, is not mediated via the androgen receptor. The absence of deleterious effects of 19-norprogesterone derivatives on metabolic parameters should favor the therapeutic use of these compounds.