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Biomedical subjects

D L Hess

Publications and source records attributed to D L Hess.

At least 37 records · Page 2Linked to original sources

Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity.

Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal-reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.

Animals↗

A bolus of recombinant human follicle stimulating hormone at midcycle induces periovulatory events following multiple follicular development in macaques.

The efficacy of follicle stimulating hormone (FSH) as an alternative to luteinizing hormone (LH)/human chorionic gonadotrophin (HCG) for the initiation of periovulatory events in primate follicles is unknown. A single bolus of 2500 IU recombinant (r)-hFSH was compared to 1000 IU r-HCG for its ability to promote oocyte nuclear maturation and fertilization, granulosa cell luteinization and corpus luteum function following r-hFSH (60 IU/day) induction of multiple follicular development in rhesus monkeys. Following the r-hFSH bolus, bioactive luteinizing hormone concentrations were <3 ng/ml. Peak concentrations of serum FSH (1455+/-314 mIU/ml; mean+/-SEM) were attained 2-8 h after r-hFSH, and declined by 96 h. Bioactive HCG concentrations peaked between 2-8 h after r-HCG and remained > or = 100 ng/ml for >48 h, while immunoreactive FSH concentrations were at baseline. The proportion of oocytes resuming meiosis and undergoing in-vitro fertilization (IVF) were comparable for r-hFSH (89%; 47+/-19%) and r-HCG (88%; 50+/-17%). In-vitro progesterone production and expression of progesterone receptors in granulosa cells did not differ between groups. Peak concentrations of serum progesterone in the luteal phase were similar, but were lower 6-9 days post-FSH relative to HCG. Thus, a bolus of r-hFSH was equivalent to r-HCG for the reinitiation of oocyte meiosis, fertilization and granulosa cell luteinization, but a midcycle FSH surge did not sustain normal luteal function in primates.

Animals↗

Hormonal induction of thumb pads and the evolution of secondary sexual characteristics of the Southeast Asian fanged frog, Rana blythii.

The fanged frogs of Southeast Asia do not express most of the hormone-dependent secondary sexual characteristics such as thumb pads that are common to other ranid frogs. At the same point in the evolutionary history of the group that these androgen-mediated characteristics are lost, male parental care first evolves. This behavior is often correlated with low androgen levels. Prior work indicates that in one of the fanged frogs, Rana blythii, adult males have low androgen levels compared to North Temperate species of Rana. This leads to the question of whether these low androgen levels are related to the unusual male parental care and the lack of expression of the thumb pad and other hormone-dependent secondary sexual characteristics in this species. We tested that hypothesis by examining the effects of exogenous dihydrotestosterone supplements on the expression of thumb pads in Rana blythii. Dihydrotestosterone injections appear to stimulate the expression of the thumb pad in R. blythii. These results support the hypothesis that low androgen levels are involved in the loss of the thumb pad in R. blythii. This work provides an example of how mapping characters on phylogenies can be a powerful approach for gaining insights into proximate physiological mechanisms of selection at the evolutionary level.

Animals↗

Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene.

BACKGROUND: In a population-based study, we examined the relationship between the risk of myocardial infarction (MI) among young women and plasma total homocysteine (tHCY), folate, vitamin B12, and a common cytosine (C) to thymine (T) polymorphism in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR). METHODS AND RESULTS: In-person interviews and nonfasting blood samples were obtained from 79 women < 45 years old diagnosed with MI and 386 demographically similar control subjects living in western Washington state between 1991 and 1995. Compared with control subjects, case patients had higher mean tHCY concentrations (13.4+/-5.2 versus 11.1+/-4.4 micromol/L, P=.0004) and lower mean folate concentrations (12.4+/-13.4 versus 16.1+/-12.2 nmol/L, P=.018). There was no difference in vitamin B12 concentrations between case patients and control subjects (346.8+/-188.4 versus 349.7+/-132.4 pmol/L, P=.90). After adjusting for cardiovascular risk factors, we found that women with tHCY > or = 15.6 micromol/L were at approximately twice the risk of MI as women with tHCY < 10.0 micromol/L (OR, 2.3; 95% CI, 0.94 to 5.64). Women with folate > or = 8.39 nmol/L had an approximately 50% lower risk of MI than women with folate < 5.27 nmol/L (OR, 0.54; 95% CI, 0.23 to 1.28). There was no association with vitamin B12 concentration. Among control subjects, 12.7% were homozygous for the MTHFR T677 allele, and these women had higher plasma tHCY and lower plasma folate than women with other genotypes. Ten percent of case patients were homozygous for the T677 allele, and there was no association of homozygosity for T677 with MI risk (OR, 0.90; 95% CI, 0.31 to 2.29). CONCLUSIONS: These data support the hypothesis that elevated plasma tHCY and low plasma folate are risk factors for MI among young women. Although homozygosity for MTHFR T677 is related to increased plasma tHCY and low plasma folate, this genetic characteristic is not a risk factor for MI in this population.

Adult↗

Alpha-adrenergic receptor antagonism and N-methyl-D-aspartate (NMDA) induced luteinizing hormone release in female rhesus macaques.

The stimulatory influence of N-methyl-D-aspartate (NMDA), a glutamate receptor agonist, on LH secretion is well established in several mammalian species including the rhesus macaque. Although the mechanism of excitation appears to involve enhanced GnRH secretion, it is unclear whether the GnRH neurons respond directly to this excitation or whether stimulatory inter-neurons are involved. This study investigated the possibility that noradrenergic afferents play a major role in mediating the response of the primate hypothalamo-pituitary reproductive axis to NMDA. In situ hybridization histochemistry, using a cRNA probe coding for the NMDAR1 receptor subunit, revealed abundant mRNA in the locus coeruleus, a brain area rich in noradrenergic neurons. Furthermore, using double-label fluorescence immunocytochemistry, the tyrosine hydroxylase immunopositive neurons of the locus coeruleus showed immunoreactivity for the NMDAR1 receptor subunit protein. A second experiment examined whether prazosin, an alpha 1-adrenergic receptor antagonist, could attenuate NMDA-induced stimulation of LH release. Prazosin (either 1 or 5 mg/kg b.wt., i.v.) was administered to female rhesus macaques during the luteal phase of the menstrual cycle, 40 min before administration of NMDA (10 mg/kg b.wt., i.v.). Regardless of the prazosin pre-treatment, plasma LH concentrations showed a significant increase (P < 0.01) within 10 min of the administration of NMDA. Therefore, in spite of the evidence that at least some of the noradrenergic neurons of the primate hindbrain express the NMDAR1 receptor subunit, it is unlikely that noradrenergic inter-neuronal pathways alone play a major role in mediating the stimulatory action of NMDA on GnRH/LH secretion in primates. Indeed, because the GnRH neurons of the rhesus macaque are located diffusely in various regions of the hypothalamus and medial-septal/preoptic area, their net response to excitatory amino acids is likely to be more complicated, involving a combination of both stimulatory and inhibitory inter-neurons, and possibly also a direct interaction.

Adrenergic alpha-Antagonists↗

Serum concentrations of steroid hormones during reproduction in the Atlantic stingray, Dasyatis sabina.

The Atlantic stingray, Dasyatis sabina, has a well-defined annual reproductive cycle in Florida. We collected adult specimens over 12 months and evaluated reproductive parameters and serum levels of five steroid hormones, 17beta-estradiol (E2), progesterone (P4), testosterone (T), dihydrotestosterone (DHT), and corticosterone (CS). Female E2 peaked twice, once in mid-March to early April in association with ovulation and again in mid-June to mid-July in association with the enlargement of a second group of ovarian follicles. Female P4 peaked in early March and early April, coincident with the peak in E2. Female DHT was variable but exhibited a pattern not clearly associated with known events in the reproductive cycle. Female T and CS levels did not vary significantly through time. In males, T, DHT, and CS increased progressively through winter and spring, peaking in March when females were ovulating and when copulation probably took place. DHT concentrations were usually at least twice T levels. These three hormones peaked long after the November/December peak in gonadosomatic index. E2 was measurable in males and was highest during the period of testicular development. Male P4 varied in a pattern not clearly associated with known reproductive events.

Animals↗

Correlation between plasma homocyst(e)ine and aortic atherosclerosis.

Plasma homocyst(e)ine [H(e)] levels correlate with the prevalence of arterial occlusive diseases. Recently, transesophageal echocardiography (TEE) has been used to evaluate patients with atherosclerotic plaques in the thoracic aorta. The purpose of this study was to determine whether H(e) levels correlate with the degree of atherosclerotic plaque in the thoracic aorta (ATH) as seen on TEE. Maximum plaque areas for three locations in the thoracic aorta (arch, proximal descending, and distal descending) were measured with TEE in 156 patients. Maximum plaque areas for these locations were added to yield an estimate of ATH. ATH and H(e) levels, and levels of folic acid, vitamin B12, and pyridoxal 5'-phosphate were measured in a double-blind manner. Univariate analysis demonstrated a significant correlation of H(e) with ATH (r = 0.3, p< 0.001). On multivariate analysis, H(e) was independently predictive of ATH (r for the model including H(e) was 0.63, p < 0.0001). Plasma H(e) levels are therefore significantly and independently correlated with the degree of atherosclerosis in the thoracic aorta.

Aged↗

Differential effects of subcutaneous estrogen and progesterone on low-density lipoprotein size and susceptibility to oxidation in postmenopausal rhesus monkeys.

OBJECTIVE: To study the differential effects of subcutaneous E2 alone or in combination with P on the susceptibility of low-density lipoprotein (LDL) cholesterol to oxidation in naturally postmenopausal diet-controlled rhesus monkeys. DESIGN: Prospective, longitudinal controlled study. SETTING: Oregon Health Sciences University, Portland, Oregon, and Oregon Regional Primate Research Center, Beaverton, Oregon. PATIENT(S): Five naturally postmenopausal rhesus monkeys. INTERVENTION(S): Estradiol was administered subcutaneously for the first 4 weeks, followed by E2 plus P for 4 weeks, followed by a third 4-week washout period. MAIN OUTCOME MEASURE(S): Changes in plasma lipoprotein levels and oxidation of LDL and serum concentrations of E2 and P. RESULT(S): Levels of LDL cholesterol fell after 4 weeks of treatment with E2, compared with baseline. The lag time to half maximal light absorbancy after 4 weeks of E2 treatment was significantly increased compared with baseline. The maximal absorbance values and the slope of the propagation phase after 4 weeks of treatment with E2 were decreased compared with baseline. After 4 weeks of combined E2 and P treatment, all values were comparable to baseline. CONCLUSION(S): These results suggest that subcutaneous E2 therapy appears to enhance LDL resistance to oxidation and that this effect is attenuated by the addition of the P.

Animals↗

Initiation of periovulatory events in gonadotrophin-stimulated macaques with varying doses of recombinant human chorionic gonadotrophin.

During in-vitro fertilization (IVF) cycles, a large bolus of human chorionic gonadotrophin (HCG) is used to induce periovulatory events, but the efficacy of lower doses is undefined. Following follicular stimulation in rhesus monkeys, oocyte nuclear maturation, IVF, granulosa cell luteinization and corpus luteum function were compared after injection of 100, 300 or 1000 IU recombinant HCG or 1000 IU urinary HCG. Bioactive HCG rose to peak concentrations within 2 h that were proportional to the dose administered (100 < 300 < 1000 IU, recombinant HCG = urinary HCG). The duration of surge values (>100 ng/ml) was also dose-dependent (0 h, 100 IU; 24 h, 300 IU; >48 h, 1000 IU, recombinant and urinary HCG). While the proportions of oocytes resuming meiosis and undergoing IVF were similar among groups, fewer animals yielded fertilizable oocytes following 100 and 300 IU (five of nine) compared to 1000 IU recombinant and urinary HCG (nine of 10). Peak values of serum progesterone in the luteal phase were similar, but declined 2 days earlier after 100 and 300 IU relative to 1000 IU recombinant and urinary HCG. Thus, 3-10 fold lower doses of HCG elicit low amplitude surges of short duration that induce periovulatory events such as re-initiation of oocyte meiosis and granulosa cell luteinization. However, oocyte fertilization and luteal function may optimally require surges of higher amplitude and longer duration similar to those produced by standard doses of 1000 IU recombinant or urinary HCG.

Animals↗

The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes.

Elevated concentration of plasma total homocysteine (tHcy) is a common risk factor for arterial occlusive diseases. Folic acid (FA) supplementation usually lowers tHcy levels, but initial tHcy and vitamin levels, multivitamin use, and polymorphisms in the gene for 5, 10-methylenetetrahydrofolate reductase (MTHFR) may contribute to variability in reduction. We tested the effects of a 3-week daily intake of 1 or 2 mg of FA supplements on tHcy levels in patients with and without coronary heart disease (CHD) who were analyzed for the C677T MTHFR mutation. Prior multivitamin intake and baseline vitamin and tHcy levels were also compared with responsiveness to folate supplementation. Both dosages of FA lowered tHcy levels similarly, regardless of sex, age, CHD status, body mass index, smoking, or plasma creatinine concentration. In non-multivitamin users, FA supplements reduced tHcy by 7% in C/C homozygotes and by 13% or 21% in subjects with one or two copies of the T677 allele, respectively; the corresponding reductions were smaller in users of multivitamins. Moreover, T/T homozygotes had elevated tHcy and increased susceptibility to high levels of tHcy at marginally low plasma folate levels, as well as enhanced response to the tHcy-lowering effects of FA. Although other factors are probably involved in the responsiveness of tHcy levels to FA supplementation, about one third of heterogeneity in responsiveness was attributable to baseline tHcy and folate levels and to multivitamin use.

Alleles↗

Effects of administration of testosterone, dihydrotestosterone, oestrogen and fadrozole, an aromatase inhibitor, on sex skin colour in intact male rhesus macaques.

For defining the mechanism of control of sex skin colour in male rhesus macaques (Macaca mulatta) by hormones, a spectrocolorimeter was used to monitor skin redness after administration of testosterone, dihydrotestosterone (a non-aromatizable androgen), oestradiol or fadrozole (an aromatase inhibitor that blocks the conversion of testosterone to oestrogen). Skin blood flow was measured by laser doppler. Eight 9-14 kg, 5-9 year old intact male rhesus macaques were given hormone, fadrozole or vehicle treatments in a cross-over experimental design. Baseline blood flow and colour measurements were taken in four paired tattoo defined areas on the back and legs of each animal (one pair in non-sex skin, three pairs in sex skin). Colour and blood flow measurements were taken 3-4 days after the first dose and, thereafter, once a week for 3-6 weeks. Measurements taken after treatments were compared with baseline and intra-animal comparisons were made between treatment and vehicle for each animal. In all animals after administration of 4 mg testosterone kg-1 (long-acting), redness in the sex skin areas increased (P = 0.032) by day 3 and returned to baseline values by day 7. Administration of 1 mg oestradiol kg-1 day-1 for 4 days caused increased redness in all animals (P = 0.007) similar in magnitude to that caused by testosterone. Administration of 0.1 mg dihydrotestosterone kg-1 day-1 for 4 days resulted in a nonsignificant decrease in redness (P = 0.09) on days 3-7. Treatment with fadrozole (0.25-0.5 mg kg-1 day-1) for 3 weeks caused sex skin to become significantly less red during treatment (P = 0.014). There was no significant change in redness in non-sex skin areas during any treatment. Sex skin blood flow increased in animals treated with testosterone, correlating with increased redness (R = 0.906), while blood flow in non-sex skin was unchanged. Increased redness after treatment with testosterone and oestrogen, no change in redness with treatment with dihydrotestosterone and a decrease in redness after treatment with fadrozole support the conclusion that oestrogen controls sex skin redness, and testosterone acts indirectly through conversion to oestrogen to cause increased sex skin redness in male rhesus macaques.

Animals↗

The role of androgens in opportunistic breeding, tropical frogs.

In this paper we present the results of an interspecific study on the androgen levels of several species of Old World tropical frogs. These data are used to test three hypotheses: (1) in unpredictable, aseasonal environments with opportunistic breeding, gonadal hormones have a permissive rather than an activating role in the expression of mating behavior (Crews and Moore, 1986), (2) a behaviorally induced androgen response is present in opportunistic aseasonal species as well as in temperate seasonal breeders (Crews and Moore, 1986; Wingfield et al., 1990), and (3) because maintenance of high plasma testosterone levels has an associated energetic and/or fitness cost (Moore and Marler, 1987; Wingfield et al., 1990), continuously breeding frogs have lower testosterone levels than seasonal, discontinuous breeders. Androgen and corticosterone levels were found to vary significantly among species exhibiting the same mating behavior, providing support for the hypothesis that hormones have a permissive role. Differences in androgen level were correlated with (1) variation in level of male-male aggression, (2) relative density of male frogs, and (3) call rate and power output of male vocalization. These results indicate that a behaviorally induced androgen response is present in opportunistic, aseasonal breeders. Furthermore, tropical, aseasonal, opportunistic breeding frogs appeared to have lower androgen levels, generally, than confamilial temperate, seasonal breeders. This difference is consistent with the hypothesis that maintenance of high plasma testosterone levels is energetically expensive.

Androgens↗

Opiatergic influence on gonadotropin-releasing hormone and luteinizing hormone release during the macaque menstrual cycle.

Concomitant fluctuations in median eminence perfusate GnRH and plasma LH occur in rhesus macaques during the periovulatory period and after ovariectomy. The association between GnRH and LH pulses during the follicular and luteal phases of the monkey menstrual cycle is less clearly defined. However, observed LH patterns suggest higher amplitude and slower pulses of GnRH in the luteal than in the follicular phase of the menstrual cycle. The present studies were planned to compare the GnRH/LH patterns in individual monkeys by simultaneous push-pull perfusion (PPP) and blood sampling during different ovarian steroid milieus. In the initial trial, placement of two push-pull cannulae (PPCs) in the median eminence and a jugular vein catheter caused immediate loss of regular menstrual cycles in 3 monkeys, although cycles resumed over 3-6 mo postoperatively. After the return of normal reproductive cycles, PPP was performed for 12 h on either Day 7, 8, or 9 of the luteal phase. The results showed an unexpected and profound decline in LH and progesterone (P4) concentrations during the initial 4 h. No pulses of LH or P4 were observed in the remaining 8 h. All 3 monkeys exhibited menstrual bleeding 2-3 days after PPP. In subsequent trials, we continuously infused the opioid receptor antagonist nalmefene (Nmf, 1 mg/h, i.v.), starting the fourth day after PPC implantation into 11 monkeys. Menstrual cycles with accompanying fluctuations of circulating estradiol-17 beta (E2) and P4 returned in less than 40 days in these macaques and continued without further Nmf treatment. Trials of 12-h PPP/blood sampling were performed during the follicular phase with (n = 4) or without (n = 4) Nmf, and during the luteal phase with (n = 6) or without (n = 3) Nmf. Endocrine data from the 3 animals without Nmf during the luteal phase were combined with the hormonal values that were obtained in the initial trial because all 6 animals exhibited similar GnRH, LH, and P4 profiles, i.e., low levels and infrequent or absent pulses. Treatment with Nmf during luteal sampling enhanced hypothalamic GnRH secretion (> 10-fold increase in mean GnRH levels over those without Nmf) and reinitiated distinctive serum LH and P4 pulses. In contrast, patterns of hypothalamic GnRH and serum LH during the follicular phase were similar with or without Nmf treatment. These GnRH/LH profiles consisted of low-amplitude hourly pulses. Collectively, the observations suggest that stress-induced activation of opiatergic neurons can inhibit the GnRH pulse generator and that these neuronal systems are more sensitive to such inhibition in the presence of elevated levels of circulating P4. However, our observation that Nmf accelerated the reinstatement of ovarian cycles after surgery, when circulating E2 and P4 were very low, suggests that GnRH secretions are influenced by activation of different opioid receptor subtypes in response to different stresses. Some of these GnRH/opioid interactions are independent of P4.

Animals↗

Sexual dimorphism in secretion of hypothalamic gonadotropin-releasing hormone and norepinephrine after coitus in rabbits.

Coital activation of the hypothalamo-hypophyseal ovarian axis (HOA) is well documented in rabbits, but coital excitation of the hypothalamo-hypophyseal testicular axis (HTA) is less well described. We and others have postulated that the response of the HOA to coitus, as characterized by a dramatic release of hypothalamic GnRH, may be mediated by an increase in norepinephrine (NE) neuronal activity. Herein, we studied selective HOA and HTA responses in New Zealand White rabbits before, during, and after coitus. Firstly, we determined the effects of microdialysis (mu D) and blood-sampling methods on plasma LH and testosterone (T) patterns in male rabbits during sexual performance. Subsequently, we compared the patterns of release in GnRH and norepinephrine (NE) from the arcuate nucleus-median eminence (AME) at 10-min intervals with changes in plasma LH levels in copulating male and female rabbits. Lastly, in 2.5-min AME mu D samples from females immediately after coitus, we measured NE and GnRH concentrations to determine whether NE release precedes that of GnRH. Tethered, freely moving rabbits were exposed to their partners for 10 min at the end of the third (10-min sampling for 5-7 h) or second (2.5-min sampling for 4 h) hour. Data from individuals that did not mate during the 10-min of pairing in the 3- to 7-h sampling trials were included as a control group (sham-mated). The results showed no changes (P > 0.05) in plasma LH and T in either mated (LH: pre, 0.13 +/- 0.08 ng/ml; post, 0.15 +/- 0.03 ng/ml; T: pre, 2.39 +/- 1.20 ng/ml; post, 0.85 +/- 0.26 ng/ml) or sham-mated males (LH: pre, 0.21 +/- 0.08; post, 0.25 +/- 0.10 ng/ml; T: pre, 1.46 +/- 0.51 ng/ml; post, 1.40 +/- 0.38 ng/ml). Likewise, coitus did not alter patterns of AME-NE (pre, 0.47 +/- 0.25; post, 0.56 +/- 0.25 ng/ml) and GnRH (pre, 0.61 +/- 0.45; post, 0.74 +/- 0.32 pg/ml) in mated or sham-mated males. The constant HTA activity during coitus in males appears to be independent of experimental manipulation per se because LH and T levels between mu D (0.18 +/- 0.05 and 1.72 +/- 0.85 ng/ml, respectively) and non-mu D (0.16 +/- 0.05 and 1.52 +/- 0.36 ng/ml, respectively) rabbits were not different (P > 0.05). In contrast to males, females displayed unambiguous and simultaneous increases in NE (P < 0.05) and GnRH (P < 0.01) release from the AME within 10-20 min after coitus; these elevated concentrations in mu D samples lasted for 3-4 h. Microdialysis NE levels averaged 0.02 +/- 0.01 ng/ml before mating, whereas postcoital values averaged 0.09 +/- 0.01 ng/ml. GnRH levels were 1.04 +/- 0.56 and 11.78 +/- 5.06 pg/ml before and after coitus, respectively. Concomitant increases in plasma LH levels were also observed after coitus in these female rabbits. Moreover, measurements of NE and GnRH in 2.5-min mu D samples revealed that the postcoital increase in NE preceded that in GnRH by 2.5-7.5 min (P < 0.05). The results suggest that neuroendocrine circuits in the two sexes of the New Zealand White rabbit respond differently to genital stimulation. In male rabbits, coitus does not alter patterns of AME NE or GnRH secretion, nor does it change the circulating levels of plasma LH or T. Conversely, in females, coitus induces the rapid release of hypothalamic NE, GnRH, and pituitary LH. The increase in coitally induced NE occurs before the rise in GnRH, which supports the hypothesis that NE is a critical neurochemical in coital activation of GnRH neurons.

Analysis of Variance↗

Recombinant human inhibin-A administered early in the menstrual cycle alters concurrent pituitary and follicular, plus subsequent luteal, function in rhesus monkeys.

Inhibin, a suppressor of pituitary FSH secretion in nonprimate species, may also act in the ovary to regulate follicular development. To examine whether inhibin has similar actions in primates, female rhesus monkeys (n = 3/treatment), exhibiting regular menstrual cycles, received sc injections of either vehicle or 60 micrograms/kg recombinant human inhibin-A at 0800 and 1600 h for 5 days beginning at menses. The vehicle-treated monkeys displayed menstrual cycles of normal length, with the follicular (11.3 +/- 2.5 days, mean +/- SE) and luteal (16.3 +/- 2.5 days) phases demarcated by midcycle peaks in serum estradiol (E) and bioactive LH. After the first inhibin injection, levels of immunoreactive inhibin A peaked at 10 ng/mL within 1 h and returned to baseline (< 0.1 ng/mL) before the second injection 8 h later. Although serum E and LH did not change, bioactive FSH decreased (to 66% of pretreatment levels, P < 0.05) within 8 h. Within 1 day, circulating bioactive FSH was less (P < 0.05) in inhibin-treated monkeys, compared with controls. By 2-3 days, serum E levels were also markedly (P < 0.05) reduced in inhibin-treated animals, whereas bioactive LH rose 3-fold (P < 0.05). After inhibin treatment, the midcycle rises in serum E and LH were delayed; hence, the follicular phase was prolonged (15.0 +/- 2.6 days, P < 0.05), compared with controls. Although the patterns and levels of serum LH circulating during the subsequent luteal phase seemed comparable in both groups, mean progesterone levels were suppressed to 2-3 ng/mL (P < 0.05) during the midluteal phase in inhibin-treated monkeys. However, the length of the luteal phase in inhibin-treated cycles (13.0 +/- 2.6 days) was not significantly altered. We conclude that exogenous inhibin rapidly diminishes pituitary FSH secretion in female monkeys during the early follicular phase of the menstrual cycle. This action, and/or other actions directly on the ovary, leads to subsequent effects on follicular steroidogenesis and pituitary LH secretion that culminate in an aberrant ovarian cycle characterized by an insufficient luteal phase. The study identifies, for the first time, possible activities and roles of inhibin during the ovarian cycle in primates.

Animals↗

Melatonin and puberty in female lambs exposed to EMF: a replicate study.

In an earlier study, we found no effects of 60 Hz electric and magnetic fields (EMF) from a 500 kV transmission line on serum melatonin patterns or on puberty in ten female Suffolk lambs (Ovis aries). We conducted a larger replicate study of 15 lambs exposed to a mean electric field of 6.3 kV/m and a mean magnetic field of 3.77 muT and 15 controls exposed to EMF two orders of magnitude weaker than in the line area. The replicate produced essentially the same results as our previous study.

Animals↗

Serum steroid hormones and the reproductive cycle of the female bonnethead shark, Sphyrna tiburo.

The bonnethead shark Sphyrna tiburo reproduces by placental viviparity with one of the shortest gestation periods (4.5-5 months) known in sharks. In southwest Florida, mating in this species occurs in November, sperm is stored until ovulation/fertilization the following March-April, and parturition occurs in August. Serum concentrations of four steroid hormones (17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone) were determined by radioimmunoassay over a complete reproductive cycle in mature females from a wild population. Serum 17 beta-estradiol and testosterone levels are high during mating and preovulatory stages. Preovulatory concentrations of testosterone are greater in female S. tiburo than in any other female elasmobranch previously studied. Progesterone levels are significantly elevated during preovulatory, ovulatory, and postovulatory stages, while serum dihydrotestosterone levels increase significantly during the preovulatory stage. Our study is the first to demonstrate a sustained rise in progesterone during gestation in a placental shark and suggests a regulatory role for this hormone during the period prior to implantation of the embryos in the uterus.

Animals↗

Relationship of smoking cessation and nicotine gum use to salivary androstenedione and testosterone in middle-aged men.

Cross-sectional studies have associated cigarette smoking in men with elevated androstenedione and little net effect on other sex steroids. However, it is not clear if such findings reflect the impact of nicotine exposure or if sex hormone levels change following smoking cessation. The relationship of the reported number of cigarettes smoked per day and salivary cotinine to salivary testosterone and androstenedione was examined in 221 men aged 35 to 59 years at baseline and 1 year following randomization into a clinical trial including a smoking-cessation intervention. At baseline, salivary cotinine was related to increased salivary androstenedione and testosterone following control for age, body mass, alcohol intake, and time of day of specimen collection (partial r = +.14 and +.30 P < .05 and .01, respectively). The reported number of cigarettes smoked per day was unrelated to either hormone. At the first annual visit, there was a significant decrease in the salivary androstenedione of men who had quite smoking and were currently using nicotine gum (94 v 60 pg/mL, P < .05, n = 34) and of men who had quit smoking and were not exposed to nicotine (86 v 56 pg/mL, P < .05, n = 48), whereas the salivary androstenedione of men who remained smokers at the first annual visit was unchanged (83 v 85 pg/mL, n = 139). Salivary testosterone levels were not significantly affected by a change in smoking status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗