The influence of body mass index, age and gender on current illness: a cross-sectional study.

CONTEXT: Obesity poses a significant health risk, but health risk is not equivalent to actual health status. Further, age and gender might alter the effect of body weight on physical health. OBJECTIVE: To determine the relationship between body mass index (BMI), age, gender and current health status. DESIGN: Data from the 1988-1994, 2003-2004 and 2005-2006 National Health & Nutrition Examination Surveys were weighted to represent the US population. BMI, age, gender and current medication use were analyzed in a sample-adjusted 9071 women and 8880 men. MAIN OUTCOME MEASURES: The percentage of participants taking medication and the total number of medications taken. RESULTS: In both the 1988-1994 and 2003-2006 data sets, with few exceptions, medication loads did not increase significantly in overweight compared with normal-weight people. Medication loads increased significantly in obese compared with normal-weight people aged 40+, but only marginally at 25-39 years. Medication loads were higher in women than men, but significantly less so in people aged 55-70. CONCLUSIONS: First, medication loads, a measure of current health status, were increased in obese compared with the normal-weight people, but the effect was mainly at ages over 40 years. In addition, BMI category contributed less to medication loads at ages 25-39 than in older groups. Second, there was little difference in current health status in normal-weight versus overweight people at all ages. Finally, higher medication loads in women than men are more apparent in younger than older people. Although obesity does not substantially affect current health in young people, it is likely that the increased medication loads in obese compared with normal-weight older people originates at least in part from an increased BMI starting at a younger age. Thus, age, gender and onset of high BMI all require consideration when using BMI to assess current health status.

Antiandrogen implanted in brain stimulates male reproductive system.

Chronic intrahypothalanic implantation of cyproterone, an antiandrogen, in male rats resulted in specific stimulation of testes, seminal vesicles, and prostates. Implantation of cholesterol-filled or empty tubes in the median eminence in controls was ineffective. We conclude that decreases in the amount of testosterone reaching specific receptors in the median eminence or in nearby regions activate a mechanism that produces increased gonadotropin secretion.

Prepubertal testosterone treatment of neonatally gonadectomized male rats: defeminization and masculinization of behavioral and endocrine function in adulthood.

Testosterone (T) administered well after the neonatal "critical" period to females at a dose approximating male levels permanently defeminizes reproductive function (see companion publication). To obtain comparable data for the male, neonatally gonadectomized (NeoGx) males received T filled or empty Silastic capsules during days 15-30 of age and were studied in adulthood. Compared to controls, the T treatment resulted in reduced lordosis and proceptive behaviors, increased mounting and intromission behaviors without differences in penile reflexes or size, and reduced plasma FSH and LH surges. Twenty of twenty-three sham-NeoGx males, but only one NeoGx male, showed ejaculatory behavior despite equivalence in penile reflexes and size after detaching a frenulum when present on the penis. These results show that T can still act on neural substrates well beyond the neonatal period to defeminize and masculinize endocrine and behavioral function in the male rat. A comparison with effects in females indicates a sex difference, the male appearing to be more sensitive to these actions of T.

Prepubertal testosterone treatment of female rats: defeminization of behavioral and endocrine function in adulthood.

This study assessed the capacity of testosterone (T) administered well after the neonatal "critical" period to permanently sexually differentiate reproductive function. Females received T filled or empty Silastic capsules during days 15-30 of age and vaginal cyclicity, ovarian weight and appearance, lordosis and proceptive behaviors, mounting behavior, and the gonadotropin response to estrogen and progesterone were measured in adulthood. T-treated females (plasma levels of 0.66 ng T/ml) showed constant vaginal estrus from the day of vaginal opening and small, polyfollicular ovaries. Proceptive behaviors were dramatically reduced whether or not the ovaries were present after day 15 of age, but lordosis behavior was not affected. Exposure to T for 5-6 h was ineffective. Compared to controls, T-treated females had dramatically reduced plasma FSH and LH surges. No effects were observed on mounting behavior, phallus size, or body weights. These results suggest that androgen at approximately male levels can act on neural substrates well beyond the neonatal period to permanently defeminize endocrine and behavioral function in the female rat.

Estrogen/progesterone treatment in adulthood affects the size of several components of the medial preoptic area in the male rat.

The results of preliminary studies suggested that steroid and/or propylthiouracil (PTU) treatment of adult gonadectomized (Gxd) male rats significantly reduced the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA). Therefore, we designed a study to examine this effect in detail. Groups of adult rats were sham Gxd (intact) or Gxd, then treated with multiple injections of oil (males and females), or estrogen and progesterone (males). Gonadectomized estrogen/progesterone-treated males had a significantly smaller SDN-POA volume, smaller volume of the medial division of the medial preoptic nucleus (MPNm), smaller volume of the anteroventral MPNm (MPNav), and larger volume of the anteroventral periventricular nucleus (AVPv). The volume of the central division of the medial preoptic nucleus (MPNc) or of the suprachiasmatic nucleus was not affected. There were no differences between Gxd estrogen/progesterone-treated males vs the group that received PTU as well, indicating that the PTU treatment was unnecessary. The reduced volume of the SDN-POA was due to a reduced volume of the MPNav and of the portion of the SDN-POA located within the MPNm-exclusive of the MPNav and MPNc. In conclusion, estrogen/progesterone treatment in adulthood caused significant changes in the volume of several medial preoptic structures in two separate groups of Gxd males. Because the steroids produced no significant effects in intact males, testicular hormones appear to "protect" these structures from the effects of the estrogen/progesterone treatment.

Cytoarchitectonic analysis of the SDN-POA of the intact and gonadectomized rat.

The densely staining group of cells referred to as the sexually dimorphic nucleus of the preoptic area (SDN-POA) is greater in volume in the male than in the female rat. Because we and others have reported absolute volumes that have been consistent within individual studies but that vary considerably, we characterized the SDN-POA by describing its morphology with respect to the cytoarchitectonic divisions of the medial preoptic nucleus (MPN) in intact and gonadectomized rats. We report three major findings: the SDN-POA is heterogeneous and is composed of cells belonging to three distinct cytoarchitectonic divisions; the cytoarchitecture of the MPN and its medial and lateral divisions (MPNm and MPNl, respectively) in male rats appear to be influenced by the hormonal status in adulthood; and a small anteroventral division of the MPN (MPNav) is present in males but virtually absent in females. Specifically, the SDN-POA is located within the MPNm, but consists of subcomponents located within the central division of the MPN (MPNc), the MPNav, and part of the MPNm-exclusive of the MPNc and MPNav. The percentage of the total SDN-POA located within the MPNc and MPNav. The percentage of the total SDN-POA located within the MPNc and MPNav was greater in males, and that in the MPNm-exclusive of the MPNc and MPNav was greater in females, indicating that the SDN-POA has a different cytoarchitectonic composition in the two sexes. Gonadectomy produced no significant differences in SDN-POA volume, but the MPN, MPNl, and MPNm were significantly reduced in gonadectomized versus intact males, suggesting an activational effect of testicular hormones on these structures.

Gonadal steroid-dependent GAL-IR cells within the medial preoptic nucleus (MPN) and the stimulatory effects of GAL within the MPN on sexual behaviors.

More GAL-I cells exist within sexually dimorphic cell groups of the medial preoptic nucleus (MPN) in male rate than females, a large percentage of estrogen-concentrating cells within MPN cell groups are also GAL-immunoreactive (GAL-IR), and significantly more GAL-IR cells are visible with estrogen or its precursor, testosterone. Gonadal steroids also increase the size (diameter) of MPN GAL-IR cells and the number of GAL-IR cell processes within a portion of the MPN called the "GAL-IR MPOA plexus," which exists in males only. GAL microinjected into the MPN stimulated male-typical sexual behaviors, with more testosterone required in females than males. Immunoneutralization with anti-GAL serum inhibited male-typical sexual behavior, indicating a role for endogenous GAL within the MPN. Microinjection of GAL into the MPN also stimulated female-typical sexual behaviors in estrogen-treated females and males, and GAL within the MPN dramatically overrode an inhibition of lordosis by dihydrotestosterone in rats of both sexes.

Distribution of galanin-immunoreactive cells within sexually dimorphic components of the medial preoptic area of the male and female rat.

A high percentage of galanin-immunoreactive (GAL-I) cells within sexually dimorphic components of the medial preoptic area (MPOA) of the rat also concentrate estrogen and GAL microinjected within the medial preoptic nucleus (MPN) facilitates masculine sexual behavior after testosterone priming. Thus, we determined the distribution of GAL-I cells within the MPOA and their response to gonadal steroids. We report significantly greater numbers of GAL-I cells within the central division of the medial preoptic nucleus (MPNc) and fewer within the anteroventral periventricular nucleus (AVPv), of the gonadectomized male than the gonadectomized female; that GAL-I cell numbers and densities within the AVPv are increased significantly in the intact, testosterone- or estrogen-treated male compared to the gonadectomized male and that GAL-I cell numbers and densities within the MPNc and GAL-I cell densities within the medial division of the MPN (MPNm), are increased significantly by gonadal steroids in rats of both sexes. The results suggest an involvement of galaninergic cells within the MPOA in the regulation of sexually dimorphic, gonadal steroid-sensitive functions.

Estrogen-concentrating cells within cell groups of the medial preoptic area: sex differences and co-localization with galanin-immunoreactive cells.

Male and female rats have approximately equal numbers of estrogen(E)-concentrating cells within the medial preoptic area (MPOA). Several cell groups within this brain region are sexually dimorphic, however, and these groups may have sexually different numbers of E-containing cells; this, in turn, may reflect sex differences in neural-regulated functions. In order to study this possibility, the distribution of E-concentrating cells was determined using estrogen autoradiography. Except for the lateral portion of the medial preoptic nucleus (MPNl), the density of E-concentrating cells was 3-5-times higher within the most medially situated cell groups of the female than the male, i.e., within the anteroventral periventricular nucleus (AVPv), periventricular preoptic area (PVPO), medial portion of the medial preoptic nucleus (MPNm), and its central portion (MPNc). In addition, we determined whether E-concentrating cells also express the neuropeptide, galanin. An average of 13% of the E-concentrating cells were galanin positive, which represented 15% of the galanin-immunoreactive population. These results demonstrate a frank and dramatic sex difference in the distribution of E-concentrating cells within sexually dimorphic regions of the MPOA, and also suggest that an interaction between galanin and gonadal steroids may be an important means by which cells within the MPOA regulate reproductive function.

Effects of testosterone and progesterone on brain 5alpha-reductase and aromatase in Long-Evans males and comparison of aromatase in Long-Evans vs. Sprague-Dawley rats.

We investigated medial basal hypothalamic-preoptic area (MBH-POA) 5alpha-reductase and aromatase enzyme activities in gonadally intact and castrated adult Long-Evans (L-E) male rats treated with testosterone (T), progesterone (P), and a combination of T+P. MBH-POA 5alpha-reductase and aromatase activities did not differ significantly among the groups. The lack of a difference in MBH-POA aromatase between control and castrated L-E animals was unexpected. In two further experiments, MBH-POA aromatase was examined in intact and castrated L-E and Sprague-Dawley (S-D) rats, using direct and indirect assays. The activity in castrated S-D (but again, not in L-E) rats significantly decreased compared to control values. These data suggest that the absence of gonads does not decrease MBH-POA aromatase in adult L-E rats.

A rat model for attention deficit-hyperactivity disorder.

A number of animal models for attention deficient-hyperactivity disorder (ADHD), a common childhood disorder, have been developed. However, none of these models are truly representative of naturally occurring developmental ADHD. In such models, hyperactivity is induced by electrical or chemical brain lesions, by pharmacological manipulation, or by genetic breeding that is coupled with hypertension. Based on the observation that some hyposexual rats also are hyperactive, we have studied these rats in order to determine whether they portray characteristics representative of ADHD. Results of open field testing, response to stimulant medication challenge, and measurement of the rat's ability to block irrelevant information in a conditioned avoidance response demonstrate three properties characteristic of ADHD: a) a high level of spontaneous motor activity; b) an attenuation of motor activity in response to amphetamine; and c) a deficit in selective attention. These data indicate that these rats may be a model for the study of ADHD.

Hyperactivity in hyposexual male rats.

It is widely accepted that some male rats fail to copulate because of a decrease in arousability, measured as decreased general locomotor activity (hypoactivity). This relationship, however, failed to explain an observation made in our laboratory that rats that failed to copulate exhibited increased general locomotor behavior. To directly address this issue, we quantified open-field and male sexual behaviors in 360 rats from two different strains. Twenty-two out of 49 hyposexual males were also hyperactive; this was a significantly greater number than would be expected by chance (p < 0.002, binomial test). Interestingly, only 6 of the 49 hyposexual males were hypoactive; this number was actually significantly smaller than would be expected by chance (p < 0.02). There was no correlation between behavioral measures and plasma levels of testosterone or progesterone. A decrease in selective attention and a failure to be stimulated by amphetamine was apparent in all hyperactive rats--those normal-sexual as well as hyposexual. The hyperactive rats were not hypertensive. We conclude that a significant percentage of hyposexual rats are hyperactive, and that hypoactive rats generally exhibit normal levels of sexual behavior. Decreased selective attention and decreased responsiveness to amphetamine do not explain this result, which is also not related to blood pressure or androgen levels.

Effects of thymectomy on reproductive function and behavior.

The effects of thymectomy in perinatal Long-Evans rat pups on their reproductive function in early adulthood were examined. Thymectomized females had decreased lordotic responsivity to estrogen, while thymectomized males exhibited differences in mount latency or postejaculatory interval; these results suggest a possible influence of the thymus on the normal development of the neural substrates of sexual behavior. Gonadal histology appeared unperturbed in rats of either sex. No statistical abnormalities in luteinizing hormone or testosterone levels were seen in male animals. Likewise, no disturbances were observed in the ability of females to exhibit normal positive feedback after estrogen and progesterone administration; negative feedback after unilateral ovariectomy (as judged by ovarian compensatory hypertrophy) was also normal. The timing of puberty was not statistically delayed in females, even though slowed growth rates were observed. A heightened surgical stress response, as judged by progesterone levels in experimental females, suggests that perinatal thymectomy may possibly alter the sensitivity of adults to stress.

Galanin microinjected into the medial preoptic nucleus facilitates female- and male-typical sexual behaviors in the female rat.

Galanin (GAL) microinjected within the sexually dimorphic medial preoptic nucleus (MPN) facilitates male-typical sexual behaviors in the male rat, a response that requires the presence of testosterone. As in the male, GAL-immunoreactive cells located within the MPN of the female also concentrate gonadal steroids and become less immunoreactive after gonadectomy. Thus, to investigate sexual behaviors in the female and to determine whether effects are comparable to those obtained in the male, GAL was microinjected unilaterally within the MPN of female rats. We report that GAL stimulated female-typical lordosis behavior after estrogen priming, and that the effect was not due to general arousal as measured by nonspecific locomotor activities. In a separate experiment, GAL microinjected within the MPN dose-responsively increased mount frequencies and decreased mount latencies in testosterone-primed females. A higher dose of testosterone was required in females for this stimulation of male-typical sexual behavior than required in a previous experiment in males.

Cholecystokinin stimulates and inhibits lordosis behavior in female rats.

Recently, IP CCK-8 has been shown to inhibit lordosis in sexually experienced, estradiol benzoate (EB) and progesterone (P) primed rats. However, receptivity is influenced by prior sexual experience and/or exposure to sex steroids, as well as the steroid dosage administered before testing. Thus, we examined the effect of CCK-8 (3 micrograms/kg; IP) on lordosis in rats with different degrees of receptivity. Three weeks after ovariectomy, females were treated with EB followed 48 hr later with P, or with EB alone. CCK-8 significantly facilitated lordosis in rats given 5 micrograms EB. Following a 5 week nonexperimental period, animals were more receptive and CCK-8 significantly inhibited lordosis in the 5 or 10 micrograms EB groups. In a separate experiment, rats were ovariectomized, adrenalectomized, and treated with EB alone. As in the first experiment, CCK-8 facilitated and inhibited lordosis. CCK-8's effects were highly dependent on the female's receptivity, facilitating lordosis when receptivity was low and inhibiting lordosis when receptivity was high (but not maximal). In conclusion, IP CCK-8 modulates lordosis behavior independent of P, but its effects depend on the female's degree of receptivity.

Effects of site-specific CNS microinjection of cholecystokinin on lordosis behavior in the male rat.

We have previously demonstrated that intracerebroventricular injections of sulphated cholecystokinin octapeptide (sCCK-8) had a dramatic facilitatory effect on lordosis behavior in the gonadectomized, estrogen-primed male rat. In the female, sCCK-8 facilitates or inhibits lordosis when microinjected into the medial preoptic nucleus (MPN) or ventromedial nucleus of the hypothalamus (VMH), respectively. In order to identify sCCK-8 responsive sites that modulate lordosis behavior in gonadectomized males, sCCK-8 was microinjected into the MPN or VMH. Sulphated CCK-8 significantly increased lordosis behavior when microinjected into the MPN of estrogen-primed males, but had no significant effects when microinjected into the VMH. These results imply that CCK-sensitive neural substrates within the MPN may act to disinhibit lordosis in the gonadectomized, estrogen-primed male rat. The lack of an effect of VMH injection of sCCK-8 on lordosis in males is discussed in terms of possible sex differences in sCCK-8-sensitive lordosis-modulating circuits.

Microinjection of galanin into the medial preoptic nucleus facilitates copulatory behavior in the male rat.

The medial preoptic area (MPOA) is an important region for masculine sexual behavior. Because galanin (GAL) immunoreactive cells within the MPOA are affected by the gonadal steroid environment and GAL binding is apparent, GAL was microinjected site specifically in 0, 10, 50, 100, and 500 ng doses in order to determine effects on copulatory behavior. Unilateral microinjection of GAL within the medial preoptic nucleus facilitated copulatory behavior in a dose-responsive fashion, evidenced by an increase in the percentage of males that displayed sexual behaviors and a decrease in mount and intromission latencies. These effects required the presence of gonadal steroids, and were not due to general arousal as measured in open field testing. The techniques of survival analysis were used to display data and for statistical analysis of intromission and mount latencies; these approaches revealed significant effects that were not evident with more commonly used procedures. The results support the suggestion that sexually dimorphic galaninergic cell groups within the MPOA are involved in gonadal steroid-induced masculine sexual behavior.

Effects of cholecystokinin on male copulatory behavior and lordosis behavior in male rats.

Because the distribution of cholecystokinin octapeptide (CCK-8) within the hypothalamus and limbic system overlaps with steroid concentrating regions, and because these areas are involved in the regulation of reproductive behaviors, we examined the effects of exogenous CCK-8 on male copulatory behavior and lordosis behavior in the male rat. Peripheral administration of a dose of CCK-8 that altered lordosis behavior in females (3 micrograms/kg, intraperitoneal) was ineffective in altering male copulatory behavior in males, either before or after gonadectomy, and was also ineffective in altering lordosis behavior after estrogen priming. In a separate experiment, CCK-8 injected into the lateral ventricle also did not affect male copulatory behavior, but lordosis behavior was increased dramatically after gonadectomy and estrogen priming. Although these results do not answer the question whether CCK-8 is acting to inhibit a neural system that normally suppresses lordosis behavior or is acting to stimulate a facilitatory circuit, these results do indicate the existence of an estrogen sensitive neural substrate in males on which CCK can act to facilitate lordosis behavior.

Microinjection of cholecystokinin into the medial preoptic nucleus facilitates lordosis behavior in the female rat.

We examined the effect of cholecystokinin (CCK) on lordosis behavior when administered into the medial preoptic area or the nucleus accumbens (NAcc) of ovariectomized estrogen-primed female rats. The frequency of lordotic responses was measured subsequent to unilateral microinjections of sulphated octapeptide CCK (sCCK-8) into the medial preoptic nucleus (MPN) or the NAcc. In the first experiment, three doses of sCCK-8 (1, 5, and 50 ng) microinjected into the MPN, and 50 ng injected into the NAcc produced a marked facilitation of lordosis. In a separate experiment, unilateral injections of an undiluted sCCK-8 antiserum into the MPN produced significant reduction in lordosis behavior in highly receptive females when compared with a normal rabbit serum injected control group. The results of the present study indicate that the CCK innervation of the MPN is involved in the neural regulation of lordosis behavior in the female rat.