Adolescent cocaine and injection stress effects on the estrous cycle

Chronic cocaine exposure during critical periods of development induces short- and long-term effects. During the pubertal period, the hypothalamic–pituitary–gonadal (HPG) axis undergoes many dynamic changes. The present study investigated whether chronic periadolescent cocaine alters reproductive maturity in the rat. Sixty female Long–Evans hooded rats were randomly assigned to one of three conditions (20 mg cocaine/kg/day, saline injected and uninjected), for dosing from postnatal day 21 (P21) through P60. Several indicators of reproductive maturation and functioning were assessed during and following treatment. Cocaine exposure had no effect on the onset of puberty or on the date of first ovulation. The number of proestrus–estrus transitions was significantly lower in cocaine-exposed females compared to uninjected females, but not compared to saline-injected controls. This reduction was observed during exposure to cocaine, as well as after the cessation of injections. During the dosing period, cocaine-exposed rats also exhibited a greater number of cycles that had no clear P–E transition than did UN subjects; this effect disappeared once injections stopped. These alterations suggest immediate, and possibly persisting, alterations in the control of ovulation after chronic cocaine exposure throughout adolescence. Interestingly, during the injection period, the saline-injected females had a significantly greater number of diestrus days compared to uninjected and cocaine-injected animals, as well as a lower proportion of regular 4- and 5-day cycles. These differences disappeared once injections stopped. These results suggest a stress-induced irregularity of the estrous cycle, possibly attenuated by cocaine and recoverable after exposure. The present findings indicate that the HPG axis is susceptible to short-term, and possibly to long-term, alterations induced by cocaine exposure throughout the adolescent period.     

Lateral ventricle injection of orexin-A ameliorates central precocious puberty in rat via inhibiting the expression of MEG3

Background: Central precocious puberty (CPP) is characterized as increasing gonadotropin-releasing hormone (GnRH) release. Orexin-A has also been shown to affect GnRH release. However, there are few reports about the effect of orexin A on the treatment of CPP. Methods: After establishing the precocious puberty model, the rats were divided into four groups: normal control, precocious puberty rats, precocious puberty rats treated with normal saline and precocious puberty rats treated with orexin-A. The vaginal opening time, second estrus cycle, ovarian index and uterus index of rats in each group were detected. qRT-PCR was performed to examine the expression of MEG3 and kisspeptin in rats. HT22 cells were transfected with pcDNA-MEG3 to detect the expression of Kisspeptin. Results: In this study, we found that orexin-A not only delayed the day of vaginal opening and regular estrus cycle days but also decreased the ovarian index and uterus index in rats with CPP. In addition, orexin-A reversed the up-regulation of MEG3 and kisspeptin in rats with CPP. In HT22 cells, the mRNA and protein level of kisspeptin were enhanced by pcDNA-MEG3. Conclusion: Our results suggest that orexin-A ameliorates central precocious puberty in rat and MEG3 might be involved in this effect, suggesting that MEG3 might be a novel target in treating central precocious puberty.     

The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.     

Sex differences in circadian timing systems: Implications for disease

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.     

Metabolic clues regarding the enhanced performance of elite endurance athletes from orchiectomy-induced hormonal changes

This article examines the metabolic performance of an elite cyclist, Lance Armstrong, before and after his diagnosis with testicular cancer. Although a champion cyclist in 1-day events prior to his diagnosis of testicular cancer at age 25, he was not a contender in multi-day endurance cycle races such as the 3-week Tour de France. His genetic makeup and physiology (high VO2max, long femur, strong heavy build) coupled with his ambition and motivation enabled him at an early age to become one of the best 1-day cyclists in the world. Following his cancer diagnosis, he underwent a unilateral orchiectomy, brain surgery and four cycles of chemotherapy. After recovering, he returned to cycling and surprisingly excelled in the Tour de France, winning this hardest of endurance events 7 years running. This dramatic transformation from a 1-day to a 3-week endurance champion has led many to query how this is possible, and under the current climate, has led to suggestions of doping as to the answer to this metamorphosis. Physiological tests following his recovery indicated that physiological parameters such as VO2max were not affected by the unilateral orchiectomy and chemotherapy. We propose that his dramatic improvement in recovery between stages, the most important factor in winning multi-day stage races, is due to his unilateral orchiectomy, a procedure that results in permanent changes in serum hormones. These hormonal changes, specifically an increase in gonadotropins (and prolactin) required to maintain serum testosterone levels, alter fuel metabolism; increasing hormone sensitive lipase expression and activity, promoting increased free fatty acid (FFA) mobilization to, and utilization by, muscles, thereby decreasing the requirement to expend limiting glycogen stores before, during and after exercise. Such hormonal changes also have been associated with ketone body production, improvements in muscle repair and haematocrit levels and may facilitate the loss of body weight, thereby increasing power to weight ratio. Taken together, these hormonal changes act to limit glycogen utilization, delay fatigue and enhance recovery thereby allowing for optimal performances on a day-to-day basis. These insights provide the foundation for future studies on the endocrinology of exercise metabolism, and suggest that Lance Armstrong's athletic advantage was not due to drug use.     

Progesterone affects sex differentiation and alters transcriptional of genes along circadian rhythm signaling and hypothalamic‐pituitary‐gonadal axes in juvenile Yellow River Carp (Cyprinus carpio var.)

Progesterone (P4) is a biologically active steroid hormone that is involved in the regulation of oocyte growth and maturation, as well as development of the endometrium and implantation in the uterus of humans. It can also stimulate oocyte maturation in female fish, as well as spermatogenesis and sperm motility in male fish. Thus, P4 has been extensively used in human and animal husbandry as a typical progestin. However, P4 remaining in the water environment will pose a potential hazard to aquatic organisms. For example, it can interfere with sex differentiation and reproduction in aquatic vertebrates such as fish. Therefore, we investigated the effects of prolonged progesterone exposure on the expression of genes related to circadian rhythm signaling and the hypothalamic‐pituitary‐gonadal (HPG) axes in Yellow River Carp, which may have a potential impact on their sex differentiation. Our results suggested that P4 exposure altered the expression of genes related to circadian rhythm signaling, which can lead to disorders in the endocrine system and regulate the HPG axes‐related activities. Furthermore, the expression of genes related to the HPG axes was also altered, which might affect gonadal development and the reproductive systems of Yellow River Carp. In addition, these changes may provide a plausible mechanism for the observed shifts in their sex ratio toward females.     

运动训练对心理应激大鼠下丘脑-垂体-性腺轴的影响

目的:探讨运动训练对心理应激大鼠下丘脑-垂体-性腺(HPG)轴的影响。方法:将50只SD大鼠随机分为对照组、运动组、急性心理应激组、慢性心理应激组、急性心理应激 运动组、慢性心理应激 运动组。运动大鼠进行10周游泳运动(1次/天,60min/次);心理应激大鼠分别施加急(一次)、慢(后3周)性心理应激。测定各组大鼠下丘脑GnRHmRNA、垂体LHmRNA表达及血清睾酮(T)、皮质醇(C)含量。结果:(1)急、慢性心理应激组大鼠下丘脑GnRH、垂体LHmRNA表达量、血清T水平均显著低于对照组,血清C水平显著高于对照组;慢性心理应激组大鼠体重、睾丸重、睾丸重/体重均显著低于对照组。(2)与对照组相比,运动组大鼠下丘脑GnRH、垂体LH表达及血清T、C均无明显变化。(3)与心理应激组比,慢性心理应激 运动组大鼠下丘脑GnRH、垂体LH表达量以及血清T水平显著升高。结论:心理应激作为一种应激源,可能会引起大鼠HPG轴紊乱;中等负荷运动对提高机体抗应激能力有一定作用。     

Gonadotrophin-Inhibitory Hormone: A Multifunctional Neuropeptide

Gonadotrophin-inhibitory hormone (GnIH) was discovered 8 years ago in birds. Its identification raised the possibility that gonadotrophin-releasing hormone (GnRH) is not the sole hypothalamic neuropeptide that directly influences pituitary gonadotrophin release. Initial studies on GnIH focused on the avian anterior pituitary as comprising the only physiological target of GnIH. There are now several lines of evidence indicating that GnIH directly inhibits pituitary gonadotrophin synthesis and release in birds and mammals. Histological studies on projections from hypothalamic GnIH neurones subsequently implied direct actions of GnIH within the brain and in the periphery. In addition to actions on the pars distalis via the median eminence, GnIH axons and terminals are present in multiple brain areas in birds, and the GnIH receptor is expressed on GnRH-I and -II neurones. Furthermore, we have demonstrated the presence of GnIH and its receptor in avian and mammalian gonads. Thus, GnIH can act directly at multiple levels: within the brain, on the pituitary and in the gonads. In sum, our data indicate that GnIH and its related peptides are important modulators of reproductive function at the level of the GnRH neurone, the gonadotroph and the gonads. Here, we provide an overview of the known levels of GnIH action in birds and mammals. In addition, environmental and physiological factors that are involved in GnIH regulation are reviewed.