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To determine the relationship between hypothalamic secretion of LRF and pituitary secretion of LH, LRF activity was estimated by a semi-quantitative bioassay and human LH was measured by radioimmunoassay in samples drawn every 5–10 inin over a 70- to 90-min period from the peripheral blood of 5 human subjects with a variety of states of gonadal function. The LRF activity bioassay was based on changes in plasma radioimmnoassayable LH in ovariectomized, estrogen and progesterone-treated rats after intravenous injection of test substance. The assay is sensitive enough to detect LRF activity in as little as 1 ml of plasma. LH levels showed episodic fluctuations in a normal male, 2 testosterone-deficient men, an estrogen-treated, castrated man, and a normal woman studied in pre and postovulatory periods. Episodic fluctuations in plasma LRF activity also occurred in samples from all subjects. Estimated from a bioassay standard curve of responses to synthetic LRH 15 samples from a normal man contained L...

To elucidate the relative importance of pituitary and hypothalamic sites of action of gonadal steroids in modifying gonadotropin secretion, the effects of gonadal insufficiency and of estrogen treatment on the secretion of LH and LH-releasing factor (LRF) were measured in men with carcinoma of the prostate and in male transsexuals. The bioassay of LRF was performed in ovariectomized rats pretreated with estrogen and progesterone, and the change in rat plasma LH from before to 10 min following iv injection of methanol extracts of 40 ml of plasma was the measure of LRF in human plasma. LRF was not detectable in 24 samples from 16 normal men nor in 14 samples from 4 men within 30 days after castration. Men sampled more than 30 days after castration had significantly elevated plasma LRF levels. Plasma LH was significantly elevated within 24 hr after castration in 4 subjects but subsequently declined in one, and then rose again as plasma LRF activity levels increased. Treatment with estrogens for peri...

To determine whether estrogen deficiency in the human leads to increased secretion of luteinizing hormone-releasing factor (LRF), bioassayable LRF activity was estimated by a semi-quantitative assay in extracts of peripheral plasma taken at random from 22 postmenopausal women whose plasma LH levels ranged from 2.7 to 22.3 ng/ml. Seven of the 36 samples tested contained LRF activity (expressed as increment in plasma LH in receipient assay rats) which was more than 3 standard deviations greater than the mean LRF activity in 26 plasma samples from 17 women during the pre- or postovulatory phase of the menstrual cycle. These findings show that LRF is detectable in the blood of some postmenopausal women. In such women, LH is also secreted episodically as shown by cyclic fluctuations in LH levels in multiple plasma samples from 4 menopausal women drawn at 10-min intervals over a 150–190 min period. In 36 plasma samples from menopausal women assayed for both LRF and LH, elevation of LRF activity occurre...

THE treatment of all types of asthma by methods based on allergic findings has proved satisfactory in our hands in about 70 per cent of the cases; in the other 30 per cent, results have been only fair or poor. In a review of 1,240 asthmaticpatients whom we have studied in our clinic during the past five years, we find that excellent or good results usually were obtained from those suffering from periodic attacks of asthma but who had periods during the year in which they were entirely free. On the other hand, fair or poor results were usually obtained in those patients who had periodic attacks of severe asthma but who also, daily between attacks, had either light attacks or raised considerable white glairy or semi-purulent mucus. Others working in the field of allergy have obtained somewhat similar results. Anderson (1), in 1932, reported good results in several cases of a series of asthmatic patients to whom he had given iodized oil intratracheally as a therapeutic measure. In 1932, Ochsner (2), who trea...

To test the hypothesis that the ovulatory surge of LH secretion in humans is induced by the release of LRF, peripheral plasma of women during the menstrual midcycle has been bioassayed for its effects on LH secretion in rats. Forty ml of plasma were serially extracted with increasing concentrations of methanol. The supernatant of each extraction was dried and redissolved in methanol. The final dry extract dissolved i n saline was assayed for LRF activity in the ovariectomized—estrogen—progesterone—thyroxine treated rat, the end point of the assay being the increase in radioimmunoassayable rat LH. I n preliminary studies this extraction method recovered all the LRF activity from porcine hypothalamic extracts added to plasma. Fifteen samples taken during the pre- or postovulatory period had low but detectable releasing effects when compared to saline controls (p < 0.025). Of 36 plasma samples taken between days 12–16, 6 specimens had LRF activity which exceeded the mean of nonovulatory responses by more tha...

The relationship among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarettes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. Our data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism. It is not clear whether nicotine or some other stimulus inherent in smoking is responsible for cortisol secretion without ACTH secretion.

Nausea was induced by having subjects smoke two high nicotine cigarettes in quick succession. Plasma levels of prolactin, adrenocorticotropic hormone, beta-endorphin/beta-lipotropin, growth hormone, arginine vasopressin, and neurophysin I increased without changes in thyroid stimulating hormone, luteinizing hormone, or follicle stimulating hormone. Nausea and pituitary hormone release correlated with high nicotine intake (smoking 2.87 mg nicotine cigarettes) but did not occur during lower nicotine intake (smoking 0.48 mg nicotine cigarettes). Individual differences in nausea and related hormonal responses may provide an objective method for predicting receptivity to smoking.

The present study explored neuropeptide responses to nicotine from smoking. Habitual smokers smoked research cigarettes of known strength under controlled laboratory conditions while blood samples were withdrawn unobtrusively for subsequent biochemical analysis. To provide a metric that reflected total nicotine intake and total neurohormonal output, data were integrated over time. Subjects were relatively unresponsive in the low-nicotine (0.48 mg) condition. In the high-nicotine (2.87 mg) condition, there were significant positive correlations between integrated plasma nicotine and plasma arginine vasopressin (r = +0.985), its carrier protein neurophysin I (r = +0.944), and beta-endorphin-beta-lipotropin (r = +0.977), but not adrenocorticotropic hormone. Data from an experiment that used an extraction step to remove beta-lipotropin corroborated the functional relationship between plasma nicotine and beta-endorphin implied by the original findings. Taking into account recent research on the role of neuropeptides in the modulation of affective states and cognitive function as well as of other CNS activity, the present findings were interpreted as strengthening the hypothesis that nicotine-stimulated neuropeptide release provides positive reinforcement for smoking.