Psoriasis y depresión: el papel de la inflamación / Psoriasis and Depression: The Role of Inflammation

La psoriasis es un proceso inflamatorio crónico y sistémico con múltiples comorbilidades. Entre las más frecuentes se encuentran las enfermedades mentales y en especial la depresión, con la que interrelacionan negativamente llegando a producir un peligroso círculo vicioso. Clásicamente se ha explicado la depresión de los pacientes con psoriasis como reactiva a factores psicosociales y el deterioro en la calidad de vida. Sin embargo, la asociación de estas dos patologías a través del proceso inflamatorio crónico ofrece una nueva hipótesis para su comprensión y tratamiento. Este enfoque incide en nuevos fármacos y la importancia del estilo de vida

Psoriasis is a chronic, systemic inflammatory disorder with multiple comorbidities. The most common comorbidities are mental disorders, especially depression, which can interact negatively with psoriasis to produce a dangerous vicious circle. Depression in psoriasis has traditionally been explained as a response to psychosocial factors and impaired quality of life. However, a new hypothesis linking depression and psoriasis through chronic inflammation offers insights that should help to understand and treat these diseases. In this approach, new drugs and lifestyle have an important role

Psoriasis and Depression: The Role of Inflammation. / Psoriasis y depresión: el papel de la inflamación.

Psoriasis is a chronic, systemic inflammatory disorder with multiple comorbidities. The most common comorbidities are mental disorders, especially depression, which can interact negatively with psoriasis to produce a dangerous vicious circle. Depression in psoriasis has traditionally been explained as a response to psychosocial factors and impaired quality of life. However, a new hypothesis linking depression and psoriasis through chronic inflammation offers insights that should help to understand and treat these diseases. In this approach, new drugs and lifestyle have an important role.

The factor structure of the General Health Questionnaire (GHQ): a scaled version for general practice in Spain.

BACKGROUND: The 28-item version of the General Health Questionnaire (GHQ-28) developed by Goldberg and Hillier in 1979 is constructed on the basis of a principal components analysis of the GHQ-60. When used on a Spanish population, a translation of the GHQ-28 developed for an English population may lead to worse predictive values. METHODS: We used our Spanish sample to replicate the entire process of construction of the GHQ-28 administered in a primary-care setting. RESULTS: Two shorter versions were proposed: one with six scales and 30 items, and the other with four scales and 28 items. CONCLUSIONS: The resulting GHQ-28 was a successful adaptation for use on the Spanish sample. When compared with the original version, only 21 items were the same. Moreover, contrary to the English version, which groups sleep problems and anxiety in the same scale, a scale with items related exclusively to 'Sleep disturbances' was found.

[Hydro-colloidal dressings which release hydro-active silver]. / Apósitos hidrocoloides liberadores de plata hidroactiva.

The study presented is a multicentric, prospective, open and comparative study designed with the objective of evaluating the performance of an antibacterial hydrocolloid dressing with hydroactivated silver (Comfeel Plata), when used to activate the healing process in wounds with high bacterial load, clinical signs of infection or malodour. Additionally, once the wound bed was appropriately prepared, a comparison in terms of efficacy was made between, on the one hand, continued treatment with the antibacterial hydrocolloid dressing, and, on the other hand, continued treatment with other dressings specifically designed for the proliferative phase of healing. Included into this study were 43 patients with chronic ulcers who were divided into two parallel treatment groups: In one group, Comfeel Plata (Coloplast AIS) was used until complete wound healing or for a maximum of 10-12 weeks, and in the second group Comfeel Plata (Coloplast A/S) was used until a clean wound bed was obtained and until the wound showed signs of positive evolution, at which moment the treatment was continued until complete healing or for a maximum of 10-12 weeks with dressings without silver designed especially for the proliferative phase of healing [Alione, Comfeel or Biatain (Coloplast AIS)]. The results obtained from the various study parameters indicate that the use of Comfeel Plata in the treatment of infected or colonized wounds prepares the wound bed and facilitates more rapid healing, and that the use of Comfeel Plata effectively reduces pain and malodour. The results indicate that once a clean wound bed is obtained, the use of a dressing without silver specifically for the proliferative phase will facilitate healing.

Apósitos hidrocoloides liberadores de plata hidroactiva / Hydro-colloidal dressings which release hydro-active silver

Se presenta un estudio multicéntrico, prospectivo, abierto y comparativo cuyo objetivo fue evaluar el rendimiento de un apósito antibacteriano de plata hidroactiva formulado sobre una base de hidrocoloide, en la activación del proceso de cicatrización en heridas con elevada carga bacteriana, signos clínicos de infección y mal olor. Por otro lado, una vez preparado el lecho ulceral, se comparó en términos de eficacia el tratamiento prolongado con plata frente al tratamiento con plata seguido de tratamiento con apósitos específicos para la fase de granulación. Se han incluido 43 pacientes con úlceras crónicas distribuidos en dos grupos paralelos de tratamiento: Comfeel® Plata (Coloplast A/S), hasta la completa cicatrización o durante un máximo de 10-12 semanas desde el inicio del tratamiento o este mismo apósito, hasta que la úlcera estuviera limpia y mostrara signos de evolución positiva hacia la cicatrización, seguido de tratamiento con apósitos sin plata específicos para la fase de granulación [Alione®, Comfeel® o Biatain® (Coloplast A/S)], hasta la completa cicatrización o durante un máximo de 10-12 semanas. Los resultados recogidos en los varios parámetros de evaluación indican que la utilización del apósito estudiado en heridas infectadas o colonizadas prepara el lecho ulceral para una cicatrización más rápida, disminuyendo tanto el olor como el dolor de forma efectiva. Los resultados indican que una vez preparado el lecho ulceral el proceso de cicatrización se ve favorecido por la utilización de un apósito sin plata específico para la fase de granulación

The study presented is a multicentric, prospective, open and comparative study designed with the objective of evaluating the performance of an antibacterial hydrocolloid dressing with hydroactivated silver (Comfeel® Plata), when used to activate the healing process in wounds with high bacterial load, clinical signs of infection or malodour. Additionally, once the wound bed was appropriately prepared, a comparison in terms of efficacy was made between, on the one hand, continued treatment with the antibacterial hydrocolloid dressing, and, on the other hand, continued treatment with other dressings specifically designed for the proliferative phase of healing. Included into this study were 43 patients with chronic ulcers who were divided into two parallel treatment groups: In one group, Comfeel® Plata (Coloplast A/S) was used until complete wound healing or for a maximum of 10-12 weeks, and in the second group Comfeel® Plata (Coloplast A/S) was used until a clean wound bed was obtained and until the wound showed signs of positive evolution, at which moment the treatment was continued until complete healing or for a maximum of 10-12 weeks with dressings without silver designed especially for the proliferative phase of healing [Alione®, Comfeel® or Biatain® (Coloplast A/S)]. The results obtained from the various study parameters indicate that the use of Comfeel® Plata in the treatment of infected or colonized wounds prepares the wound bed and facilitates more rapid healing, and that the use of Comfeel® Plata effectively reduces pain and malodour. The results indicate that once a clean wound bed is obtained, the use of a dressing without silver specifically for the proliferative phase will facilitate healing

Gene expression of the insulin-like growth factor system during postnatal development of the rat pituitary gland.

Insulin-like growth factors I and II (IGFI and II) are synthesized by anterior pituitary cells and participate in cellular growth and differentiation, as well as the control of pituitary hormone secretion. Type 1 and 2 IGF receptors (IGFR1 and IGFR2) and the six IGF binding proteins (IGFBPs), which modulate IGF effects, are expressed in the anterior pituitary gland. We used in situ hybridization to analyse the temporal expression pattern of IGFI and II, IGFR1 and 2 and IGFBP1-6 in the anterior pituitary gland during postnatal development in both male and female rats (10, 20, 30, 40 and 60 days of age). We found all of the components of the IGF system to be expressed in the anterior pituitary gland, with each having a specific temporal pattern of expression. In addition, there exist differences between the sexes in the expression of some components of the IGF system. These data emphasize that in the anterior pituitary gland the IGF system is under tight regulation during postnatal life when this gland continues to develop. The distinct temporal expression of each member of the IGF system may indicate specific roles in the development and physiology of the anterior pituitary gland.

Patrones de uso ambulatorio de los antiguos y nuevos antidepresivos en pacientes geriátricos con depresión / Prescription patterns of older and newer antidepresants for geriatric depresive out-patients

Objetivos: Estudio del uso real que se hace de los medicamentos antidepresivos, en un episodio depresivo en población anciana, por parte de los psiquiatras de una red ambulatoria de salud mental. Material y método: Revisión de la evolución y manejo farmacológico de un episodio depresivo índice en 150 ancianos atendidos en el Área 11/Hospital 12 de Octubre de Madrid. Estudio de la eficacia de las distintas moléculas y la necesidad de cambios farmacológicos y estrategias de potenciación a lo largo del tratamiento en el episodio índice. Resultados: Demográficos: 75 por ciento mujeres. Edad media: 72,4 por ciento. Depresión mayor: 71 por ciento. Inicio tardío: 41 por ciento. Como primera opción los grupos terapéuticos más utilizados fueron: ISRS (48,6 por ciento) y tricíclicos (45 por ciento) y las moléculas: fluoxetina 26 por ciento, mianserina 13 por ciento y paroxetina 10 por ciento. Esta primera elección del tratamiento produjo una remisión satisfactoria en el 32,9 por ciento de los casos. El 53,3 por ciento de los casos precisó sólo un cambio de molécula, 23 por ciento recibió sólo dos moléculas, 16 por ciento tres, 5 por ciento cuatro y 11 por ciento cinco o más. En el primer cambio de molécula, el ISRS inicial fue sustituido por otro ISRS en el 48 por ciento de los casos y por un tricíclico en el 30 por ciento y en el caso de los tricíclicos éstos volvieron a ser utilizados como segunda opción en el 45 por ciento y se cambió a un ISRS en el 33 por ciento. Los patrones de uso de los tricíclicos y de los ISRS fueron básicamente semejantes y se utilizaron en la misma proporción, aunque globalmente las moléculas más utilizadas fueron fluoxetina, fluvoxamina y paroxetina. En ambos grupos las tasas de remisiones y de supresiones por intolerancia o ineficacia fueron similares, pero los tricíclicos se utilizaron en mayor proporción a medida que se efectuaban más cambios. (AU)

[Prescription patterns of older and newer antidepressants for geriatric depressive out-patients]. / Patrones de uso ambulatorio de los antiguos y nuevos antidepresivos en pacientes geriátricos con depresión.

OBJECTIVE: To study the prescription patterns of antidepressants for an elderly population. METHODS: 140 out-patients suffering an index depressive episode were studied and followed for at least one year. RESULTS: Demografics: 75% women. Mean age: 72.4%. Mayor depression: 71%. Late-onset: 41%. The most frequently used types the frist choice were SSRIs (48.6%) and Tricyclics (45%), the molecules initially most prescribed: Fluoxetine (26%), Mianserin (13%) and Paroxetin (10%). Initial choice of treatment achieves satisfactory remission in 32.9% of the cases. 57% of patients needed a frist malecule switch, 23% received only two molecules, 16% three, 5% four and 11% five molecules or more. After the first switch, the initial SSRI was substituted by another SSRI in 48% of the cases and by a Tricyclic in 30%. Initial Tricyclic chaged to a SSRI in 33% and another Tricyclic in 45%. The patterns of Tricyclics and SSRIs use were not essentially different and both were used globally in the same proportion, although the most prescribed molecules were Fluoxetine, Fluvoxamine and Paroxetine. Both groups achieved statistically similar number of remissions and suppressions by intolerance or ineficcacy but tricyclics were increasingly used from the frist switch onwards.

Cellular composition of the adult rat anterior pituitary is influenced by the neonatal sex steroid environment.

Growth hormone (GH) and prolactin (PRL) secretion differ significantly between adult males and females and this is due, at least in part, to the postpubertal hormone environment which affects GH and PRL gene expression, as well as somatotrope and lactotrope proliferation. However, the role of the neonatal steroid environment in this phenomenon is less well understood. We have used in situ hybridization to determine the number of GH and PRL mRNA containing cells, as well as the level of expression of these two hormones and of the pituitary transcription factor 1 (Pit-1). Neonatally castrated male rats that had been exposed to testosterone during the neonatal period, adulthood or during both periods, males castrated as adults, normal adult males and normal proestrous females were used. Orchidectomy of adult rats had no effect on the number of somatotropes or lactotropes, but significantly reduced GH and PRL mRNA levels. Neonatal castration significantly reduced the percentage of somatotropes and increased that of lactotropes in the adult male. In addition, GH and Pit-1 mRNA levels were reduced significantly, but PRL mRNA levels were not modified. Treatment of neonatally castrated males with testosterone during the neonatal period significantly increased the percentage of somatotropes and decreased the percentage of lactotropes compared to vehicle-treated animals. It also increased GH and Pit-1 mRNA levels, but did not affect PRL mRNA levels. Adult testosterone treatment significantly increased the percentage of both somatotropes and lactotropes, as well as GH, PRL and Pit-1 mRNA levels. Treatment of neonatally castrated males with testosterone during both the neonatal and adult periods returned the percentage of somatotropes and lactotropes, as well as GH, PRL and Pit-1 mRNA levels, to that of the intact male. These results suggest that, although the postpubertal steroid environment is important in determining anterior pituitary hormone synthesis and cellular composition, the neonatal steroid environment also plays an important role in this phenomenon.

The IGF system during fetal-placental development of the mouse.

Insulin-like growth factors (IGF-I and -II) promote cellular mitosis and differentiation and have been implicated in fetal and placental growth. Together with the IGF receptors and IGF binding proteins (IGFBPs) they form a complex network, with tissue specific activity. This review will discuss the data generated to elucidate the functions of the IGF system during mouse development.

Sexually dimorphic interaction of insulin-like growth factor (IGF)-I and sex steroids in lactotrophs.

Anterior pituitary hormone secretion is sexually dimorphic due partially to gender differences in the postpubertal hormone environment; however, differences in the pituitary's responsiveness to these signals may also play a role. We have used simple and double in situ hybridization to determine whether lactotrophs and somatotrophs from male and female rats respond differently in vitro to growth hormone-releasing hormone (GHRH), somatostatin (SS) or insulin-like growth factor (IGF)-I and whether sex steroids modulate these responses. Cultures were treated with either 17 beta-estradiol (E; 10(-9)M), testosterone (T; 10(-7)M), dihydrotestosterone (DHT; 10(-7) M) or vehicle in combination with either GHRH (10(-7)M), SS (10(-7)M), IGF-I (10(-7)M) or vehicle. Basal mRNA levels of GH, prolactin (PRL) and pituitary transcription factor-1 (Pit-1) did not differ between the sexes. The responses to peptide hormones alone were similar between the sexes, but not in the presence of gonadal steroids. In females, DHT reduced and E increased the stimulatory effect of GHRH and inhibitory effect of SS on GH mRNA levels (two-way ANOVA: P < 0.05), while having no effect in males. An additive effect of E and GHRH on PRL mRNA levels was seen only in males. The E induced rise in PRL mRNA levels was completely inhibited by SS in females, but only partially so in males (two-way ANOVA: P < 0.001). IGF-I inhibited the E induced rise in PRL and lactotroph Pit-1 mRNA levels only in females. These results suggest that sex steroids modulate the pituitary's response to hypothalamic and circulating factors differently in males and females and that this may play a role in generating the sexually dimorphic patterns of pituitary hormone secretion.

Sex steroid effects on the development and functioning of the growth hormone axis.

1. The secretory pattern of growth hormone (GH) is sexually dimorphic in the adult rat. However, this difference between the sexes does not become apparent until after the onset of puberty, suggesting that pubertal sex steroids play an important role in the manifestation of this phenomenon. 2. We have addressed the question as to whether there exists a sexual dimorphism in the hypothalamic neuropeptides that regulate GH release from the anterior pituitary, i.e., somatostatin (SS) and growth hormone-releasing hormone (GHRH). In addition, we have investigated whether the developmental changes in the GH secretory pattern are correlated with changes in these neuropeptides. The effect of testosterone treatment on SS and GHRH neurons during both the neonatal period and adulthood have also been studied. 3. We have found that the synthetic capacity, as reflected in relative messenger RNA (mRNA) levels, of both SS and GHRH neurons changes throughout development in both male and female rats. These mRNA levels are sexually dimorphic at certain times during maturation and can be modulated by changes in testosterone levels, suggesting that sex steroid modulation of these two neuropeptide systems could at least partially account for the sexual dimorphism seen in the adult GH secretory pattern. 4. The neonatal steroid environment has also been suggested to be involved in the generation of the final adult GH secretory pattern, although the mechanisms underlying this effect are even less well understood. In support of the hypothesis that the neonatal steroid environment plays an important role in organizing the GH axis, we have found that the number of GHRH neurons in the adult brain, as well as their sensitivity to adult steroids, is modulated by neonatal testosterone treatment. The number of SS neurons in the periventricular and paraventricular nuclei were not modulated by neonatal steroids; however, the synthetic capacity of these neurons does appear to be influenced by the neonatal steroid environment. 5. These studies suggest that both the neonatal and adult sex steroid environments influence the adult GH secretory pattern by modulating GHRH and SS neurons.

Ontogeny of pituitary transcription factor-1 (Pit-1), growth hormone (GH) and prolactin (PRL) mRNA levels in male and female rats and the differential expression of Pit-1 in lactotrophs and somatotrophs.

Pituitary transcription factor-1 (Pit-1 or GHF-1), a transcription factor specific to the anterior pituitary, is involved in the expression and regulation of the growth hormone (GH) and prolactin (PRL) genes. Post-pubertally, the expression of both GH and PRL becomes sexually dimorphic with males having higher GH levels and females higher PRL levels; however, little is known about the postnatal regulation of their common transcription factor. Furthermore, whether the Pit-1 gene is differentially expressed in somatotrophs and lactotrophs remains to be elucidated. In this study, we used in situ hybridization histochemistry to examine Pit-1, GH and PRL mRNA levels in the anterior pituitaries of male and female rats throughout development (0, 5, 10, 20, 30, 40 and 60 days of age) to determine when GH and PRL production becomes sexually dimorphic and if this is accompanied by a dimorphism in Pit-1 gene expression. In addition, the level of Pit-1 mRNA was determined separately in both GH mRNA and PRL mRNA containing cells during the various developmental stages. We found that in both males and females the mRNA levels of Pit-1, GH and PRL remain relatively unchanged until around the time of pubertal onset (30-40 days) when there is a significant increase in all three mRNA species, which is followed by a decrease to adult levels. Also around the time of puberty, both GH and PRL mRNA levels become sexually dimorphic, with males having higher levels of GH mRNA and females higher PRL mRNA levels. In contrast, at no time during development were overall Pit-1 mRNA levels found to differ between the sexes. However, when Pit-1 mRNA content was measured separately in specific cell types, significant differences between the sexes became evident. Throughout development Pit-1 mRNA levels are higher in lactotrophs of females than in those of males, whereas in somatotrophs males have higher Pit-1 mRNA levels than females. Furthermore, within a sex there is differential expression of Pit-1 in the two cell types with females having significantly higher levels of Pit-1 in lactotrophs than in somatotrophs and males having higher levels in somatotrophs than in lactotrophs. These data support the hypothesis that a sexual dimorphism exists in the expression and pituitary specific transcription factor Pit-1; however, this dimorphism is not manifest as a difference in overall mRNA levels, but in the differential expression of this gene in lactotrophs and somatotrophs.

In vivo and in vitro regulation of pituitary transcription factor-1 (Pit-1) by changes in the hormone environment.

Pituitary transcription factor-1 (Pit-1 or GHF-1) is a transcription factor specific to the anterior pituitary and is involved in the expression and regulation of the growth hormone (GH), prolactin (PRL) and thyroid-stimulating hormone (TSH) beta-subunit genes. The expression of these three genes can be modulated by changes in the hormone environment and it is thought that some of these effects are mediated through Pit-1, but little is known about the physiological regulation of this transcription factor. Therefore, we first asked whether Pit-1 gene expression is modified as a result of changes in the in vivo gonadal steroid environment and if this could be correlated with changes in GH and/or PRL mRNA levels. Secondly, we sought to determine if sex steroids affect the mRNA levels of these three peptides by acting at the level of the pituitary and whether these effects are androgen or estrogen mediated. Finally, how sex steroids modulate the response of these three genes to the hypothalamic neuropeptides growth hormone-releasing hormone (GHRH) and somatostatin (SS) was analyzed. To this end, we compared Pit-1, GH and PRL mRNA levels in the anterior pituitary of intact, castrated, and castrated testosterone-replaced adult male rats. In addition, primary cultures of adult male pituitaries were used to study the direct effects of both androgens and estrogens on Pit-1, GH, and PRL mRNA levels. In situ hybridization histochemistry was used to compare relative levels of Pit-1, GH and PRL mRNA. Densitometric analysis of the in vivo studies showed that castration resulted in a 57, 40 and 55% decline in Pit-1, GH and PRL mRNA signal levels, respectively. Furthermore, replacement with testosterone (T) at the time of castration completely prevented the decline in all three mRNA species (ANOVA: Pit-1 mRNA, p < 0.0001; GH mRNA, p < 0.0001; PRL mRNA, p < 0.0001). In vivo, both T (10(-7) M) and estradiol (10(-9) M) were capable of stimulating Pit-1 mRNA and PRL mRNA levels, while dihydrotestosterone (DHT; 10(-7) M) had no effect. There was no effect of any of these steroid treatments on GH mRNA levels in vitro. Addition of GHRH to the cultures increased GH mRNA levels, as well as those of Pit-1 and PRL, and SS had the opposite effect on GH mRNA levels. Whereas the GH response to GHRH was not significantly modified by exposure to sex steroids, the effect of SS was. The presence of sex steroids was capable of modifying the Pit-1 and PRL responses to both GHRH and SS. These results clearly indicate that changes in circulating levels of sex steroids modulate the expression of Pit-1 in the anterior pituitary and that these changes can be correlated with commensurate modifications in GH and PRL mRNA levels. Furthermore, the effect on both Pit-1 and PRL mRNA levels occurs, at least in part, at the level of the anterior pituitary and is an estrogen-receptor-mediated event. In contrast, the effects of gonadal steroids on GH mRNA levels are less direct and are most likely mediated at the level of the hypothalamus, as well as through modulation of the response of the somatotroph to hypothalamic factors. We conclude that the transcription factor Pit-1 is actively regulated physiologically and may be involved in mediating some of the effects of sex steroids and hypothalamic factors on the synthesis of certain anterior pituitary hormones.

Growth hormone secretion in children with normal variants of short stature.

Pulsatile growth hormone (GH) secretion plays a central role in human growth during the prepubertal period of life. In order to investigate whether or not short stature in prepubertal children with normal variants of short stature (NVSS) may be explained, at least in part, by the presence of abnormalities in the pulsatile pattern of GH secretion, we have studied the spontaneous secretion of GH/24 h in 139 prepubertal children with short stature (< or = -2 SD) and normal growth velocity (> -1 SD) and in 37 prepubertal children with normal height and growth velocity. All of the subjects included in this study exhibited a body mass index (BMI) lower than 1 SD. The patients with short stature were divided into three groups according to their bone age and the existence of familial antecedents of short stature. These groups were: (1) familial short stature without bone age retardation (FSS-1); (2) constitutional, nonfamilial short stature, with bone age retardation suggesting further delay of puberty (possible constitutional delay of growth and puberty), and (3) familial short stature with bone age retardation (FSS-2). Spontaneous GH secretion was analyzed by using a computerized mathematical algorithm of pulsatility (Cluster). In addition, in all of the patients with short stature, the GH secretory response to three different pharmacological stimuli was evaluated, including: clonidine, growth hormone-releasing hormone (GHRH) and hypoglycemia after insulin administration. The mean values of GH/24 h exhibited a wide range of distribution (1.4-7.8ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of the neonatal and adult sex steroid environments on the organization and activation of hypothalamic growth hormone-releasing hormone and somatostatin neurons.

The secretory pattern of GH is markedly sexually dimorphic in the adult rat, a phenomenon that becomes manifest around the time of pubertal development. This event is due partially to the pubertal rise in gonadal steroids. However, the fetal and neonatal sex steroid environments also play an important role in generating this sexual dimorphism. Hypothalamic mRNA levels of GH-releasing hormone (GHRH) and somatostatin (SS), two neuropeptides implicated in the control of GH release, are sexually dimorphic in both neonatal and adult animals and, at least in the adult animal, are responsive to modulation by sex steroids. In this study, we examined the effects of neonatal testosterone on the number of GHRH and SS neurons in the adult hypothalamus as well as its effects on the responsivity of these neurons to later increases in sex steroids. To address these questions, male rats were either castrated or sham castrated on the day of birth (P0); these animals, along with intact females, received an injection of either testosterone or vehicle. At 60 days of age, half of each group received a Silastic capsule containing testosterone, and half received a sham implant. Growth rates were monitored throughout the study. At 75 days of age, animals were killed, and in situ hybridization to detect GHRH and SS mRNA containing neurons was performed. The number of GHRH neurons in the arcuate nucleus and ventromedial hypothalamus and the number of SS neurons in the periventricular nucleus and paraventricular nucleus were counted. Using a computerized image analysis system, GHRH and SS mRNA signal levels in individual neurons were also measured. Both neonatal and adult steroid treatments significantly increased growth rates. Those animals exposed to neonatal testosterone had significantly more detectable GHRH neurons than those that received only vehicle [P < 0.0001, by analysis of variance (ANOVA)]. Neonatal testosterone treatment had no effect on GHRH mRNA levels. Adult testosterone treatment, while having no effect on GHRH neuron numbers, stimulated GHRH mRNA levels in both males and females (P < 0.0001, ANOVA), but the magnitude of the increase depended upon whether the animal had been exposed to testosterone during the neonatal period. In contrast, the number of SS neurons was not affected by either steroid treatment. However, both treatments modulated SS mRNA levels (P < 0.0001, by ANOVA), with neonatal testosterone treatment alone resulting in significantly higher levels of SS mRNA in the adult animal. Adult testosterone treatment also significantly increased SS mRNA levels, and this was independent of previous exposure to sex steroids.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of the neonatal sex steroid environment on growth hormone-releasing hormone and somatostatin gene expression.

The growth hormone (GH) secretory pattern changes significantly throughout development in both male and female rats, becoming markedly sexually dimorphic after pubertal onset. This observation suggests that pubertal sex steroids play a role in the manifestation of this phenomenon. The neonatal steroid environment has also been shown to be intricately involved in the generation of the final adult GH secretory pattern, but the mechanisms underlying this effect remain unknown. We have addressed the question as to whether the developmental changes in the GH secretory pattern are correlated with changes in the hypothalamic neuropeptides that regulate its release from the anterior pituitary, i.e., somatostatin (SS) and growth hormone-releasing hormone (GHRH). The effects of neonatal testosterone and adult testosterone treatments on these two neuropeptide systems have also been studied. We have found that the synthetic capacity, as reflected in relative messenger RNA (mRNA) levels, of both SS and GHRH neurons changes throughout development in both male and female rats. These mRNA levels are also sexually dimorphic at certain times during maturation and, at least in the adult male, can be modulated by changes in testosterone levels. In support of the hypothesis that sex steroids play a role in the organization of the developing hypothalamus, we have shown that both estradiol and testosterone promote the survival of hypothalamic neurons in vitro. Preliminary in vivo studies indicate that the neonatal sex steroid environment may influence the number of GHRH neurons that are found in the adult brain, as well as their sensitivity to adult steroids.(ABSTRACT TRUNCATED AT 250 WORDS)