RESUMEN
PURPOSE: We examined the mechanism by which neonatal immune stress reduces the sexual behavior of female rats in adulthood. METHODS: Neonatal female rats were randomly divided into 3 groups: control (n = 11), postnatal day 10 lipopolysaccharide (PND10LPS) (n = 23), and PND25LPS (n = 11) groups, which received intraperitoneal injections of LPS (100 µg/kg) or saline on PND10 and 25. Daily inspections of the vaginal opening (VO) were performed from PND27 to PND37. Thereafter, the frequency of estrus was assessed for 15 days. Female rats (at 11-12 weeks of age) were placed in a cage with male rats, and their sexual behavior was monitored for 30 min. The hypothalamic mRNA expression levels of factors related to sexual behavior were examined via real-time PCR. RESULTS: VO occurred later and the frequency of estrus was lower in the PND10LPS group compared to the control group. The number of lordosis behaviors and the total number of mounts performed by male partners were lower in the PND10LPS and PND25LPS groups than in the control group. Acceptability: The lordosis quotient and lordosis rating were lower in the PND10LPS group than in the control group. Proceptive behavior: the number of ear wiggling events was lower in the PND10LPS group than in the other groups, and the number of hops/darts was lower in the PND10LPS group than in the control group. The hypothalamic mRNA expression level of progesterone receptors (PR)A + B was lower in the PND10LPS group than in the control group, and the hypothalamic PRB mRNA expression level was lower in the PND10LPS and PND25LPS groups than in the control group. CONCLUSION: Neonatal immune stress impeded sexual behavior and hypothalamic PR mRNA expression in female rats. Decreased progesterone activity in the hypothalamus might explain the reduction in sexual behavior seen in these rats.
Asunto(s)
Hipotálamo/metabolismo , Lipopolisacáridos/administración & dosificación , Receptores de Progesterona/genética , Conducta Sexual Animal/efectos de los fármacos , Conducta Sexual Animal/fisiología , Estrés Fisiológico/inmunología , Factores de Edad , Animales , Animales Recién Nacidos , Regulación hacia Abajo/efectos de los fármacos , Esquema de Medicación , Femenino , Expresión Génica/efectos de los fármacos , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/fisiopatología , Lipopolisacáridos/farmacología , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Receptores de Progesterona/metabolismo , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genética , Factores de TiempoRESUMEN
PURPOSE: It is known that various types of stress in early life increase the incidence of diabetes, myocardial infarctions, and psychiatric disorders in adulthood. We examined the mechanism by which neonatal immune stress reduces sexual behavior in adult male rats. METHODS: Male rats were randomly divided into 3 groups: the control (n = 17), postnatal day 10 lipopolysaccharide (PND10LPS) (n = 31), and PND25LPS (n = 16) groups, which received intraperitoneal injections of LPS (100 µg/kg) or saline (injection volume: ≤0.1 ml/g) on postnatal days 10 and 25. In experiment 1, male rats (age: 11 to 12 weeks) were put together with female rats in a one-to-one setting for mating, and sexual behavior (mounting, intromission, and ejaculation) was monitored for 30 minutes. The serum levels of luteinizing hormone (LH) and testosterone (T) and the hypothalamic mRNA expression levels of factors related to sexual behavior were examined. After experiment 1 finished, the remaining 37 male rats were used for experiment 2: the control group (n = 8), PND10 LPS group (n = 21) and PND25LPS group (n = 8) these rats had been given an i.p. injection of the saline during the expriment1. All of the rats were orchidectomized at 14 weeks of age. After a 3-week recovery period, a silastic tube containing crystalline T was subcutaneously implanted into the back of each rat. The rats' sexual behavior, serum hormone concentrations, and hypothalamic mRNA expression levels were assessed. RESULTS: In experiment 1, preputial separation occurred significantly later in the PND10LPS group than in the control group. The frequency of sexual behavior was significantly lower in the PND10LPS group than in the control group. The serum T concentrations of the PND10LPS and PND25LPS groups were significantly lower than that of the control group, but the serum LH concentrations of the 3 groups did not differ significantly. The hypothalamic mRNA expression levels of progesterone receptor B (PRB) and gonadotropin-releasing hormone (GnRH) were significantly lower in the PND10LPS and PND25LPS groups than in the control group, whereas the hypothalamic PRA + B mRNA expression levels of the 3 groups did not differ significantly. In experiment 2, after T supplementation the frequency of sexual behavior was significantly lower in the PND10LPS and PND25LPS groups than in the control group, although there were no significant differences in the serum T or LH concentrations or the hypothalamic PRB, PRA + B, or GnRH mRNA expression levels of the 3 groups. CONCLUSION: In male rats, immune stress in the early neonatal period delayed sexual maturation, reduced sexual behavior, suppressed the serum T concentration, and downregulated the hypothalamic mRNA expression levels of GnRH and the PR in adulthood. The delayed sexual maturation was presumed to have been caused by the reduction in the serum T concentration. However, the rats that experienced neonatal stress exhibited reduced sexual behavior irrespective of their serum T concentrations.
Asunto(s)
Andrógenos/metabolismo , Trastornos del Desarrollo Sexual/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Hormona Liberadora de Gonadotropina/metabolismo , Receptores de Progesterona/metabolismo , Estrés Psicológico/metabolismo , Factores de Edad , Andrógenos/genética , Animales , Animales Recién Nacidos , Trastornos del Desarrollo Sexual/inducido químicamente , Trastornos del Desarrollo Sexual/patología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hormona Liberadora de Gonadotropina/genética , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Lipopolisacáridos/farmacología , Hormona Luteinizante/sangre , Hormona Luteinizante/genética , Masculino , ARN Mensajero/metabolismo , Ratas , Receptores de Progesterona/genética , Estrés Psicológico/patología , Testosterona/sangre , Testosterona/genéticaRESUMEN
Infectious, psychological and metabolic stresses in the prenatal and early neonatal period induce long-lasting effects in physiological function and increase the risk of metabolic disorders later in life. We examined the sexual behavior of female rats that were subjected to undernutrition in the prenatal period. Eight pregnant rats were divided into two groups: a maternal normal nutrition group (mNN; nâ¯=â¯4) and a maternal undernutrition group (mUN; nâ¯=â¯4), which received 50% of the daily food intake amount of the mNN group from gestation day 13 to delivery. Nine and seven female offspring were randomly selected from the mNN and mUN groups, respectively. Vaginal opening (VO), estrous cycle length, sexual behavior and mRNA expression levels of the factors that regulate sexual behavior were observed. In the mUN group, VO day was later, the estrous cycle was longer, and the lordosis quotient and lordosis rating were lower than in the mNN group; such differences were not seen in other sexual performances, such as ear wiggles, darts, kick bouts and box. The hypothalamic mRNA expression level of progesterone receptor (PR) Aâ¯+â¯B and oxytocin (OT) were significantly lower in the mUN group than in the mNN group. These findings indicated that prenatal undernutrition disrupted puberty onset, the estrous cycle, sexual behavior and hypothalamic mRNA expression of PR and OT in female rat pups.
Asunto(s)
Desnutrición/complicaciones , Efectos Tardíos de la Exposición Prenatal/patología , Conducta Sexual , Amígdala del Cerebelo/metabolismo , Animales , Peso Corporal , Ingestión de Alimentos , Ciclo Estral , Femenino , Hipotálamo/metabolismo , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Maduración SexualRESUMEN
The effects of androgens on gonadotropin-releasing hormone (GnRH) secretion in females have not been fully established. To clarify the direct effects of androgens on hypothalamic reproductive factors, we evaluated the effects of chronic testosterone administration on hypothalamic GnRH regulatory factors in ovariectomized (OVX) female rats. Both testosterone and estradiol reduced the serum luteinizing hormone levels of OVX female rats, indicating that, as has been found for estrogen, testosterone suppresses GnRH secretion via negative feedback. Similarly, the administration of testosterone or estradiol suppressed the hypothalamic mRNA levels of kisspeptin and neurokinin B, both of which are positive regulators of GnRH, whereas it did not affect the hypothalamic mRNA levels of the kisspeptin receptor or neurokinin-3 receptor. On the contrary, the administration of testosterone, but not estradiol, suppressed the hypothalamic mRNA expression of prodynorphin, which is a negative regulator of GnRH. The administration of testosterone did not alter the rats' serum estradiol levels, indicating that testosterone's effects on hypothalamic factors might be induced by its androgenic activity. These findings suggest that as well as estrogen, androgens have negative feedback effects on GnRH in females and that the underlying mechanisms responsible for these effects are similar, but do not completely correspond, to the mechanisms underlying the effects of estrogen on GnRH.
Asunto(s)
Dinorfinas/metabolismo , Hipotálamo/efectos de los fármacos , Kisspeptinas/metabolismo , Neuroquinina B/metabolismo , Testosterona/farmacología , Animales , Dinorfinas/genética , Estradiol/farmacología , Femenino , Hipotálamo/metabolismo , Kisspeptinas/genética , Leptina/sangre , Hormona Luteinizante/sangre , Neuroquinina B/genética , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Ratas Wistar , Receptores de Kisspeptina-1/genética , Receptores de Kisspeptina-1/metabolismo , Receptores de Neuroquinina-3/genética , Receptores de Neuroquinina-3/metabolismoRESUMEN
In females, estrogens play pivotal roles in preventing excess body weight (BW) gain. On the other hand, the roles of androgens in female BW, appetite, and energy metabolism have not been fully examined. We hypothesized that androgens' effects on food intake (FI) and BW regulation change according to the estrogens' levels. To evaluate this hypothesis, the effects of chronic testosterone administration in ovariectomized (OVX) female rats with or without estradiol supplementation were examined in this study. Chronic testosterone administration decreased BW, FI, white adipose tissue (WAT) weight, and adipocyte size in OVX rats, whereas it increased BW, WAT weight, and adipocyte size in OVX with estradiol-administered rats. In addition, chronic testosterone administration increased hypothalamic CYP19a1 mRNA levels in OVX rats, whereas it did not alter CYP19a1 mRNA levels in OVX with estradiol-administered rats, indicating that conversion of testosterone to estrogens in the hypothalamus may be activated in testosterone-administered OVX rats. Furthermore, chronic testosterone administration decreased hypothalamic TNF-α mRNA levels in OVX rats, whereas it increased hypothalamic IL-1ß mRNA levels in OVX with estradiol-administered rats. On the other hand, IL-1ß and TNF-α mRNA levels in visceral and subcutaneous WAT and liver were not changed by chronic testosterone administration in both groups. These data indicate that the effects of chronic testosterone administration on BW, FI, WAT weight, and adipocyte size were changed by estradiol treatment in female rats. Testosterone has facilitative effects on BW gain, FI, and adiposity under the estradiol-supplemented condition, whereas it has inhibitory effects in the non-supplemented condition. Differences in the responses of hypothalamic factors, such as aromatase and inflammatory cytokines, to testosterone might underlie these opposite effects.