Predictive factors for the outcome of emotional and/or behavioural disorders in 18- to 48-month-old children after parent-child psychotherapy: Protocol of a European prospective cohort study.

OBJECTIVES: Several studies have shown that in young children, behavioural and/or emotional disorders are more difficult to manage than regulatory disorders. Moreover, data are lacking on outcome predictive factors. This article presents a short synthesis of previous research about outcome predictive factors in child psychiatry. It also describes the protocol of a longitudinal observational European multicentre study the main objective of which was to identify predictive factors of behavioural and emotional disorder outcome in toddlers after parent-child psychotherapy. The secondary objectives were to study predictive factors of the outcome in parents (anxiety/depression symptoms) and parent-child relationship. METHOD: In order to highlight medium-effect size, 255 toddlers (age: 18 to 48 months) needed to be included. Outcomes will be assessed by comparing the pre- and post-therapy scores of a battery of questionnaires that assess the child's symptoms, the parents' anxiety/depression, and the parent-child relationship. Multivariate linear regression analysis will be used to identify predictive factors of the outcome among the studied variables (child age and sex, socio-economic status, life events, disorder type, intensity and duration, social support, parents' psychopathology, parents' attachment, parent-child relationships, therapy length and frequency, father's involvement in the therapy, and therapeutic alliance). EXPECTED RESULTS AND CONCLUSION: This study should allow identifying some of the factors that contribute to the outcome of externalizing and internalizing disorders, and distinguishing between pre-existing and treatment-related variables. It should also help to identify children at higher risk of poor outcome who require special vigilance on the part of the therapist. It should confirm the importance of therapeutic alliance. TRIAL REGISTRATION: ID-RCB 2008-A01088-47.

Bereavement and reactions of grief among children and adolescents: Present data and perspectives.

Losing a loved one is among the most common and stressful traumatic events that a child or and adolescent can experience and can be associated with mental health and somatic disorders, as well as a range of life issues and potentially negative outcomes that may impact longitudinal development. Complicated grief, a disorder that has been studied primarily among adults, has received increasing recognition among children and adolescents in recent years. The demonstration of the distinctive character of grief reactions in relation to major depressive disorder and posttraumatic stress disorder has resulted in the inclusion of "persistent complex bereavement disorder" in an annex section of DSM-5 and of "prolonged grief disorder" in ICD-11. The grieving process in children and adolescents is not linear and is often characterised by periods of regression. Developmental phases should be taken into account to understand and clinically describe grief reactions occurring during childhood and adolescence. There are currently numerous interventions for bereaved children and adolescents, but little evidence to support them. More research focusing on the understanding of the underlying mechanisms and the risk factors for complicated grief among children and adolescents, as well as the implementation of evidence-based interventions, is definitely warranted.

[Early restrictive feeding disorders: Quantitative assessment of parent/infant feeding interactions]. / Troubles du comportement alimentaire restrictif du nourrisson et du jeune enfant : évaluation quantitative des interactions parent/nourrisson pendant le repas.

INTRODUCTION: Interest in the study of early feeding disorders (FD) has steadily increased during recent decades. During this period, research described the importance of the transactional relationships and the complex interplay between caregiver and child over time. On the basis of the previous studies, our study tried to explore the associations between the characteristics of the parents and the temperamental characteristics of the infants with early FD. GOALS: A first aim of the present study was to show if parental perception of child temperament (including ability for arousal self-regulation) and parental characteristics (emotional and eating attitudes) are associated with early FD. A second aim was to identify emotional/behavioral difficulties in children with early FD by comparing children with a normal development and children with a diagnosed FD, and to investigate whether there are any correlations between parental emotional and feeding characteristics and a child's eating and emotional-behavioral development. A final aim was to explore if feeding conflict is bound to both infant ability for arousal self-regulatation and caregiver emotional status during meals. METHOD: Participants: 58 clinical dyads (children aged 1-36 months) and 60 in the control group participated in the study. The sample of 58 infants and young children and their parents was recruited in a pediatric hospital. They were compared to healthy children recruited in several nurseries. PROCEDURE: all parent-child pairs in the clinical sample were observed in a 20-minute video-recording during a meal using the procedure of the Chatoor Feeding Scale. After the videotaping, parents completed a battery of self-report questionnaires assessing their child's and their own psychological symptom status. MEASURES: Child's malnutrition assessment was based on the Waterlow criteria. The Child Behavior Checklist (CBCL 1½-5) was used to assess a child's emotional/behavioral functioning. The Infant Behavior Questionnaire-Revised (IBQ-R), a widely used parent-report measure of infant temperament, was used to identify the structure of infant temperament. The Eating Attitude Test-40, a self-report symptom inventory, was used to identify concerns with eating and weight in the adult population. The Chatoor Feeding Scale was used to assess mother-child feeding interactions during a meal based on the analysis of the videotaped feeding session. RESULTS: Analyses revealed that children with FD did not have a difficult temperament, especially no disability for arousal of self-regulatation, but their emotional-behavioral functioning is characterized by internalizing problems. Analyses of the EAT-40 showed that mothers of the children diagnosed with FD had significantly higher scores than mothers of the control sample; it means these mothers showed more dysfunctional eating attitudes. In addition, meals were characterized by negative effects in parents in the clinical group. When compared to the control sample, the feeding interactions between children with FD and their parents were characterized by low dyadic reciprocity, high maternal non-contingency, great interactional conflict and struggles with food. However, no significant correlation emerged either between the severity of malnutrition in infants or the conflict during feeding. CONCLUSION: Our study confirms the relations established in previous research. Finally, future longitudinal studies are needed to further clarify and investigate others factors that may be involved in early feeding disorders.

[Asperger syndrome in contemporary fictions]. / Le syndrome d'Asperger dans les œuvres de fiction actuelles.

BACKGROUND: During recent years, fictions featuring a character with Asperger syndrome have been increasingly produced in literature, cinema and TV. Thus, the public has gradually discovered the existence of this specific category of autism spectrum, which is far removed from old popular representations of autistic disorders, often associated with mental retardation. OBJECTIVES: To describe the reactions generated by these characters in order to identify their major functions and also to try to explain their recent increase in fictions. METHODS: First, we explored international publications concerning this topic. A group of experienced clinicians systematically examined works of fiction produced between 2000 and 2010 that included a character with Asperger syndrome. More than 30 productions have been identified and analyzed using a method adapted from focus group. RESULTS: Over 30 productions have been recorded and analyzed. The reactions generated by these characters are described. They range from fascination to empathy; if these heroes sometimes induce laughter (because of comedy situations), they also lead us to question our vision of the world and ask ourselves about notions such as difference, normality and tolerance. We illustrate this phenomenon with examples from literature, cinema or television. DISCUSSION: Four hypotheses are proposed trying to explain the recent multiplication of these fictional characters with Asperger syndrome. The first puts forward authors' informative and educational motivations, these authors being aware of this issue. The second is supported by the "hero" concept, which has evolved gradually into the figures of the scientific world and the so-called "Geek" community. The third hypothesis, a metaphorical one, considers these heroes as symbols of a future society: a hyper systematized society, devoid of empathy, as if to warn of a risk of evolution of humanity toward a generalized mental blindness. The fourth and last hypothesis explores the personal resonance, supported by identification mechanisms. CONCLUSION: The dissemination of such fictional characters and their specific characteristics helps make Asperger syndrome a cultural component of our modern society. Such a wide distribution, supported or even promoted by associations, could contribute to better information and therefore to greater acceptance of these persons who frequently experience releases and harassment. Whatever the fate of Asperger syndrome in future classifications, the multiplication and the success of fictional productions demonstrate a growing and probably irreversible enrollment in popular culture.

The psychological effects of COVID-19-related containment in children: The E-COCCON French study.

The first containment of the Sars-Cov2 pandemic had the potential to generate posttraumatic stress (PTS) symptoms in children. OBJECTIVE: The main objective of the study was to determine the prevalence of PTS symptoms within 6 weeks of the end of lockdown, in children contained between March 17, 2020 and May 11, 2020 in France. MATERIAL AND METHODS: This was a French prospective cross-sectional study between May 15 and July 2, 2020 conducted via telephone survey. Parents of children aged between 8 and 15 years were eligible. The invitation to participate was proposed through social networks (Instagram and Facebook), various local and national media, and by e-mail to the staff of our University Hospital Center. The PTS symptoms were assessed using the CRIES-13. A score of 30 and over has been confirmed as the cut-off for screening cases. RESULTS: During the study period, 379 children (male, n = 207) were included, their mean age was 10.8±2.1 years. Symptoms of PTSD were identified in 17% of the children (girls 20.5%, boys 13.5%). These children were younger (p = 0.04), lacked access to a private outdoor space (p < 0.0001; OR: 7.8), had parents whose profession exposed them more to the coronavirus, and had parents who were more afraid of COVID-19. CONCLUSION: After the first lockdown related to the pandemic crisis, children developed PTSD symptoms. The onset of such symptoms is correlated with gender, age, lockdown conditions, and parental perceptions. These last considerations were worse for pink- or blue-collar families, attesting to the subsequent intensification of health inequalities.

[Preventive staff meetings in maternity ward for women at high medico-psycho-social risk: Qualitative study between 2012 and 2018]. / Réunions pluridisciplinaires en maternité pour les femmes à haut risque médico-psycho-social : étude qualitative entre 2012­2018.

OBJECTIVE: To assess the effectiveness of a multidisciplinary consultation meeting created in collaboration between a perinatal psychiatry team and professionals from a level 3 maternity hospital, whose purpose is to prepare the delivery and postpartum of pregnant women at high medico-psycho-social risk. I) Study the functioning of these multidisciplinary meetings. II) Assess the concordance between the decisions made in antenatal care and the actual management of the delivery and postpartum care. METHODS: This is a retrospective study of 140 files for which the opinion of the multidisciplinary meeting was requested in the years 2012, 2014, 2016 and 2018. We looked at the psychiatric files of the patients, as well as the summary sheets written after staff meetings. RESULTS: The selection of files is compliant in 98% of cases and the traceability of information in the summary sheet is over 80% for half of the process indicators. The overall compliance rate between the decisions taken at meetings and their implementation in the post-partum period is 68%. Acute psychiatric episode and reporting could be anticipated. CONCLUSION: This multidisciplinary consultation meeting is efficient in the early detection of risk situations. The decisions taken during the multidisciplinary meetings in antenatal care are mostly applied postpartum in the Maternity Ward. In cases where they are not applied, the system offers great reactivity to postpartum professionals.

[HIV Disclosure to the Child/Adolescent in Central and West Francophone Africa]. / Annonce à l'enfant et à l'adolescent de son statut VIH en Afrique francophone centrale et de l'Ouest.

We report the attitudes and practices of health care workers involved in the disclosure process to adolescents living with HIV (ALHIV) in a network including West and Central African French-speaking countries, and the experiences of young living with HIV (YLHIV). During a three-day workshop in Abidjan, Côte d'Ivoire, caregivers (doctors, psychologists, social workers) from 19 pediatric HIV treatment sites shared their practices and difficulties, and four YPLHIV their own disclosure experience. Thirty five participants from eight West/Central African countries (Benin, Burkina Faso, Ivory Coast, Cameroon, Mali, Democratic Republic of Congo, Senegal, Togo) contributed: 14 doctors, eight psychologists, six counselors, three social workers. The experience of the centers was variable, but the age at disclosure was late: 34% of 1296 adolescents between 10 and 12 years of age knew their status. The median age at disclosure was 13 years (range: 11-15 years). The practice of the disclosure was often complex, because of multiple factors (fear of the parents of the breaking of the secrecy, lack of communication between professionals). The individual disclosure was the main practice. Four centers practiced HIV disclosure in group sessions to facilitate mirror support, and one used peer-to-peer support. YPLHIV have advocated for an earlier disclosure, from 10 years. In West and Central Africa, the process of HIV disclosure remains complex for parents and caregivers, and occurs too late. The development of a good practice guideline for HIV disclosing adapted to socio-cultural contexts should help to improve this process.

Nous rapportons les attitudes et pratiques des soignants en Afrique francophone concernant l'annonce du statut VIH aux adolescents, et les témoignages de jeunes vivant avec le VIH (jvVIH). Lors d'un atelier de trois jours à Abidjan, Côte d'Ivoire, en novembre 2016, les soignants (médecins, psychologues, travailleurs sociaux) de 19 sites de prise en charge pédiatrique du VIH ont partagé leurs pratiques et difficultés et 4 jvVIH leur vécu de l'annonce. Au total, 35 participants de 8 pays d'Afrique de l'Ouest/centrale (Bénin, Burkina Faso, Côte d'Ivoire, Cameroun, Mali, République démocratique du Congo, Sénégal, Togo) ont contribué : 14 médecins, 8 psychologues, 6 conseillers, 3 travailleurs sociaux. L'expérience des centres était variable, mais l'âge à l'annonce restait tardif : 34 % des 1 296 adolescents âgés entre 10 et 12 ans connaissaient leur statut. L'âge médian à l'annonce était de 13 ans (étendue : 11-15 ans). La pratique de l'annonce s'avérait complexe, en raison de multiples facteurs (crainte des parents de la rupture du secret, manque de communication entre professionnels). L'annonce individuelle était la pratique majoritairement adoptée. Quatre centres pratiquaient une annonce en séances de groupe pour faciliter le soutien en miroir, et un avait recours à l'appui de pairs-adolescents. Les jvVIH ont plaidé pour une annonce plus précoce, dès 10 ans. En Afrique de l'Ouest/centrale francophone, le processus de l'annonce reste complexe pour parents et soignants, et l'annonce trop tardive. L'élaboration d'un guide de bonnes pratiques de l'annonce du VIH, adapté aux contextes socio-culturels devrait permettre d'améliorer ce processus.

Potent inhibitory effect of a new antiestrogen (RU 16117) on the growth of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.

At the daily dose of 24 mug for a period of 4 weeks, RU 16117 (11alpha-methoxyethinyl estradiol), a new antiestrogen, led to 65% reduction of the number of already established dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Not only the tumor number but also the tumor size was reduced by RU 16117 in a manner similar to that seen after ovariectomy. The absence of an inhibitory effect of doses of 0.1 to 12.5 mug 17beta-estradiol (E2) per day, a dose-range which covers the low estrogenic activity of the RU 16117 doses used, suggested that the inhibitory effect of RU 16117 was not due to its estrogenic activity. Decreased levels of receptors for E2, progesterone, and prolactin were found in the tumors remaining after ovariectomy; treatment with the dose of RU 16117 sufficient to inhibit tumor growth (24 mug) had a similar inhibitory effect on the levels of E2 and prolactin receptors. These data suggested that a reduction of hormone receptor levels in the tumor tissue could be a mechanism by which RU 16117 acts as a potent inhibitor of the growth of DMBA-induced mammary carcinoma.

PIP: The new antiestrogen RU 16117, at doses of 8 or 24 mcg daily, had been shown to completely prevent the development of rat mammary cancer when given from the day after 7,12-dimethylbenz(a)anthracene (DMBA) administration. This study was undertaken to investigate the effect of this compound on the growth of DMBA-induced tumors which had already developed in Sprague-Dawley rats. The effect was compared with that of castration. Levels of receptors for 17beta-estradiol (E2), progesterone, and prolactin (PRL) were correlated with the response. At about 3 months after DMBA administration animals with palpable tumors were selected. The rats were then treated daily for 4 weeks with .1, .5, 2.5, or 12.5 mcg E2 or with 2, 8, or 24 mcg RU 16117 injected in .1 ml of 1% gelatin in .9% NaCl. Controls were injected with the vehicle alone. For comparison, a group of rats were ovariectomized. After 4 weeks' treatment rats were killed, blood collected, and a cytosol was prepared from tumor tissues. Binding assays and radioimmunoassays were done. 8 and 24 mcg doses of RU 16117 led to 45 and 65% inhibition of tumor number, respectively, and tumor size was markedly reduced. Lower doses had less effect. Ovariectomy had an effect similar to that of 24 mcg RU 16117. E2 doses did not change the number or size of tumors. Decreased levels of receptors for E2, progesterone, and PRL were found in the tumors remaining after ovariectomy. The 24 mcg dose of RU 16117 had a similar effect on levels of E2 and PRL receptors. It was considered likely that RU 16117 exerts its inhibitory activity at both the hypothalamic-pituitary and tumor levels.

Unique steroid congeners for receptor studies.

To determine the hormone-dependence of a tumor, it is preferable to use highly specific radiolabeled ligands when available, since often more than one class of steroid hormone receptor is present in the tissue specimen, and interference from classes other than the one under study cannot be readily eliminated. In this study, we describe a simple in vitro system used to define the molecular requirements for a highly specific interaction between a steroid and the receptor corresponding to a single class of hormone. It is based on the use of homogenate or crude 105,000 X g supernatant prepared from the target organs considered as end points in routine biological potency tests and on the use of available radioligands not bound by plasma proteins (tags) to single out the receptors. For each receptor singled out in the target organ cytoplasm, the ability of over 700 molecules to decrease bound radioactivity was compared to that of the natural hormone (relative binding affinity) with the use of a dextran-coated charcoal technique to separate bound from unbound steroid. On the basis of the results on 81 molecules, presented in this study, the effect of various substituents on the affinity and specificity of the natural hormones was determined. Molecules interacting markedly with several receptors were submitted to X-ray crystallography in order to establish whether overlap between the various conformations of the natural hormone and of the test molecule might not partly account for lack of specificity.

High inhibitory activity of a new antiestrogen, RU 16117 (11alpha-methoxy ethinyl estradiol), on the development of dimethylbenz(a)anthracene-induced mammary tumors.

From the first day of dimethylbenzanthracene administration, daily treatment with 8 or 24 mug of the new antiestrogen 11alpha-methoxy ethinyl estradiol (RU 16117) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after dimethyl benzanthracene administration). At daily doses of 0.5 and 2.0 mug RU 16117, the tumor incidence was reduced to 78.6 and 40%, respectively. Not only was the number of animals developing tumors reduced after injection of low doses of RU 16117, but the number of tumors per rat and the size of tumors were also markedly reduced. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 mug RU 16117, while the binding of growth hormone and insulin was not affected. Whereas plasma luteinizing hormone levels decreased after treatment with 8 or 24 mug RU 16117, plasma prolactin levels slightly increased in animals receiving the highest dose of the antiestrogen. It is thus likely that the potent inhibitory effect of RU 16117 on the development of dimethylbenzanthracene-induced mammary tumors results from actions at both the hypothalamic-pituitary and the tumor (mammary gland) levels, the action at the peripheral level possibly being secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.

Long-Term Outcomes of ADHD: A Systematic Review of Self-Esteem and Social Function.

OBJECTIVE: To compare the long-term self-esteem and social function outcomes of individuals with untreated and treated ADHD across childhood, adolescence, and adulthood. METHOD: A systematic search of 12 databases was performed to identify peer-reviewed, primary research articles, published January 1980 to December 2011, reporting long-term self-esteem and/or social function outcomes (≥2 years; life consequences distinct from symptoms) of individuals with untreated or treated ADHD. RESULTS: Overall, 127 studies reported 150 outcomes. Most outcomes were poorer in individuals with untreated ADHD versus non-ADHD controls (57% [13/23] for self-esteem; 73% [52/71] for social function). A beneficial response to treatment (pharmacological, nonpharmacological, and multimodal treatments) was reported for the majority of self-esteem (89% [8/9]) and social function (77% [17/22]) outcomes. CONCLUSION: Untreated ADHD was associated with poorer long-term self-esteem and social function outcomes compared with non-ADHD controls. Treatment for ADHD was associated with improvement in outcomes; however, further long-term outcome studies are needed.

[Feeding disorders in infants and toddlers: At-risk situations and predisposing factors]. / Troubles du comportement alimentaire restrictifs du nourrisson et du jeune enfant : situations à risque et facteurs favorisants.

Feeding disorders and food refusal can be found in 25% of infants, with a minority of them having an organic explanation. Failure to thrive and/or severe malnutrition are found in 3-5% of infants in this population. The objective of this study was to analyze the risk factors of feeding disorders in infants and children less than 3 years of age. This study was conducted from January 2011 to December 2014 and included 103 children, 57 with feeding and/or eating disorders and 46 healthy children considered to be normal eaters. Parents participated in a structured interview and completed a data sheet to record the mode of delivery, neonatal status, medical history, milk feeding, and medical treatment. Statistical analysis indicated that cesarean delivery, prematurity, neonatal diseases, history of eating disorders in the family, consumption of protein hydrolysates, and treatment with proton pump inhibitors were highly significant risk factors in children with eating disorders. In the present study, we showed that several prenatal and postnatal conditions or interventions were associated with the development of eating disorders in young children. Recommendations for future studies include identifying environmental risk factors and implementing prevention programs focused on family, caregivers, as well as healthcare professionals. The objective is to allow physicians to efficiently sort out the wide variety of conditions, categorize them for therapy, and when necessary refer patients to specialists in the field.

[Self-evaluation of the quality of life of children aged 6 to 12 years old: construction and first steps in the validation of kidlQol, a generic computer-based tool]. / Auto-evaluation de la qualité de vie d'enfants de 6 a 12 ans: construction et premières etapes de validation du KidlQol, outil générique présenté sur ordinateur.

The KidlQol is a self-evaluation computer-based instrument to assess the quality of life of children aged 6 to 12 years old. This self-evaluation comprises three areas of their subjective quality of life: physical, psychological and social. A computer-assisted tool, composed of 62 items, was developed and set up based upon the results from the evaluation of the initial prototype tool which underwent a series validation steps, tested among children with and without psychological problems. This evaluation lead to the production of a final tool called KidlQuol, which is composed of 44 items. This tool, which utilises computer images to represent real-life situations, is adapted for and accessible to children with a French cultural background aged between 6 and 12 years old. As a generic tool, it could be used among a population of children with various types of handicaps, chronic diseases or psycho-social difficulties.

[Self-evaluation of the quality of life of children aged 6 to 12 years old: analysis of the concept and development of a prototype tool]. / Auto-evaluation de la qualité de vie d'enfants de 6 à 12 ans: analyse du concept et élaboration d'un outil prototype.

The objective of this work was to assess the quality of life of children aged 6 to 12 years old. The authors present the different conceptual and operational steps which lead to the construction of a prototype tool. It was a generic tool composed of 63 items which covered the classically described areas of life. Its originality was due to the method of construction used which included children's involvement, to the pictorial representation of real-life situations for children, and to its adaptation for gender. The evaluation of this tool showed a good level of acceptability but statistical analysis revealed some metrological inadequacies leading to the reconsideration of the initial concepts and their methods of exploration. Therefore a new tool was constructed whose validation is presented in a second article in the next issue.

Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading.

BACKGROUND: To compare histological feature of prostate cancer (PCa) according androgenic status in patients who underwent radical prostatectomy (RP). METHODS: Between March 2007 and September 2013, we prospectively analysed 937 patients who were referred to our centre for RP. Clinical, pathological and biological data have been prospectively collected. Preoperative total testosterone (TT) and bioavailable testosterone (BT) serum determinations were carried out. The threshold for low serum testosterone was set at TT<3 ng/ml. Preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern were determined in prostate biopsies and in prostate tissue specimens, crosschecked by two uro-pathologists. RESULTS: Nine hundred and thirty-seven consecutive patients were included. In all, 14.9% patients had low TT in the population. An exact match between biopsy and prostate specimens in GS grading was observed for 50.6% patients (n=474). Also, 40.9% of all patients were upgraded (n=383): 45.3% (n=63) in low serum testosterone patients and 40.1% (n=320) in normal serum testosterone patients. For prostate specimens, the proportion of patients with predominant Gleason pattern 4 was higher in patients with low TT compared with normal TT (41.7% vs 29.1%, P=0.0029). In all, 20.1% were upgraded from predominant Gleason pattern 3 on biopsies specimen to predominant Gleason 4 pattern on the prostate specimen in patients with low TT, whereas 11.6% were upgraded for normal TT patients (P=0.002). CONCLUSIONS: Low serum testosterone is an independent risk factor for predominant Gleason pattern 4 on prostate specimen after RP and for upgrading from low- to high-grade cancer between prostate needle biopsies and RP specimen. This observation should be taken into account in localised PCa management, especially for active surveillance or when a nerve-sparing approach is considered.

Characterization and hormonal control of the androgen receptor in the hamster sebaceous glands.

The costovertebral organs [CVO] and seminel vesicles [SV] of the hamster exhibit high saturable androgen uptake. The physicochemcal characteristics of the cytoplasmic androgen receptor present in these tissues have been determined and compared to those obtained in rat prostate[P]. Using the synthetic androgen R 1881 [methyltrienolone] as a radioactive ligand, it has been shown that the affinity of this compound for the cytosol CVO receptor [Kd = 0.7 +/- 0.1 nM] is similar to that for the crytosol SV receptor [Kd = 2.4 +/- 0.9 nm] in hamsters and the cytosol P receptor [Kd = 0.6 +/- 0.1 nM] in rats. The hormonal specificity of binding in these tissues is restricted to androgens. Moreover, testosterone and dihydrotestosterone have the same relative binding affinity in CVO and SV compared to R 1881. Following castration, the total number of androgen sites, as measured by an exchange assay with R 1881, decreases rapidly and parallels with a fall in lipogenic activity. Administration of an androgen rapidly restores binding capacity.

Adrenocorticotropin analogs and glucocorticoids in the hypophysectomized rat. II. Effects on cerebral cortex polyribosomes.

The capacity of free polyribosomes from rat cerebral cortex to incorporate labeled amino acids into protein (polyribosome activity) was compared in normal, hypophysectomized, and treated hypophysectomized rats. Polyribosome activity was measured in a cell-free system using a pH 5 supernatant from sham-operated rats. The polyribosome activity of hypophysectomized rats was 10-20% less than that of sham-operated rats. Subcutaneous treatment of hypophysectomized rats daily for 10 days with ACTH, corticotropic ACTH fragments [10-2- microgram of ACTH-(1-24), ACTH-(1-23), or Hoe 433 (ACTH-(1-17))], or glucocorticoids (1 mg corticosterone or 10 microgram dexamethasone) stimulated activity to a level 25-50% higher than that in sham-operated rats. Polyribosome aggregation, as measured by sucrose density gradient analysis, was also greater in treated hypophysectomized rats than in sham-operated rats. On the other hand, a daily sc dose of 100 microgram of the noncorticotropic fragment, ACTH-(1-10), did not stimulate brain polyribosome activity in hypophysectomized rats but merely restored it to the level observed in sham-operated rats. The present study suggests that stimulation of cerebral protein synthesis by ACTH and corticotropic ACTH analogs may be partly due to their ability to promote adrenal steroid secretion. Their stimulatory effect and that of glucocorticoids might explain their physiological roles during stress and learning.

Adrenocorticotropin analogs and glucocorticoids in the hypophysectomized rat. I. Effects on liver polyribosomes and rough endoplasmic reticulum.

Hypophysectomy decreased polyribosome aggregation and activity in rat liver. Polyribosome aggregation was measured by sucrose density gradient analysis and polyribosome activity was determined by the incorporation of labeled amino acids into protein in a cell-free system using pH 5 enzymes from sham-operated rats. Hypophysectomy also totally disorganized the rough endoplasmic reticulum of hepatocytes, as shown by electron micrographs. The sc administration of the ACTH fragments, Hoe 433 (corticotropic) and Org 2766 (noncorticotropic), and of glucocorticoids (dexamethasone or corticosterone) to hypophysectomized rats restored these parameters to the levels recorded in sham-operated rats in a dose-dependent fashion 5 h after injection; the effects were maintained until at least 24 h. The sc administration of the noncorticotropic but metabolically less stable fragment, ACTH-(1-10), had only a partial effect. The potency of a noncorticotropic ACTH fragment (Org 2766) in hypophysectomized rats suggests that ACTH may act on liver protein synthesis without the intervention of glucocorticoids or pituitary hormones.