Family history of alcoholism in women with generalized anxiety disorder who have premenstrual syndrome: patient reports of premenstrual alcohol consumption and symptoms of anxiety.

This study sought to determine whether family history of alcoholism is related to patient reports of premenstrual alcohol consumption and whether family history of alcoholism is related to severity of anxiety-related symptoms, in women who suffer simultaneously from both premenstrual syndrome and generalized anxiety disorder. Fifty-four women with generalized anxiety disorder and prospectively demonstrated premenstrual syndrome were questioned about family history of alcoholism and alcohol consumption patterns across the menstrual cycle. Seventy-six percent of the sample reported having an alcoholic first- or second-degree relative. Furthermore, 74% of those women having a paternal-side family history of alcoholism, but only 22% of those without such a family history, reported increased alcohol consumption premenstrually. Forty-one of these women were assessed by means of psychiatric rating scales during both the premenstrual and follicular phases of the menstrual cycle. During the premenstrual, but not the follicular, phase of the menstrual cycle, women with a paternal-side family history of alcoholism experienced more severe anxiety-related somatic, but not psychic, symptoms of anxiety, than those without such a family history. These findings suggest that family history of alcoholism may be related to premenstrual alcohol consumption patterns and to the severity of premenstrually experienced somatic symptoms of anxiety in women with premenstrual syndrome, and that these women may be self-medicating with alcohol.

The influence of premenstrual syndrome on ratings of anxiety in women with generalized anxiety disorder.

During the premenstrual and follicular phases of the menstrual cycle, 41 women who had generalized anxiety disorder (GAD) plus premenstrual syndrome (PMS) were assessed with psychiatric rating scales and compared with 21 GAD patients without PMS and 19 controls. The latter two groups were rated only once, in the typical open-ended manner. Symptoms during both phases of the menstrual cycle were more severe in the GAD + PMS patients than in the controls and were more severe during the premenstruum. For the GAD + PMS patients, ratings obtained in the typical open-ended manner were influenced by how patients felt during the premenstruum. Thus, the assessment of women with GAD + PMS may be complicated by cyclical fluctuations in symptom severity, and ratings obtained in the typical manner may be influenced disproportionately by how these patients feel premenstrually.

Thyrotropin-releasing hormone-induced contraction of urethral and vaginal muscle.

Pressure studies were carried out in 10 women to determine whether TRH stimulates muscular contractions in the genitourinary system. TRH (500 micrograms) or saline was administered iv as a bolus injection. Whereas saline had no effect, TRH increased intraurethral pressures in all women, vaginal pressure in 7, and bladder pressure in none. These findings suggest that TRH, acting centrally, peripherally, or both, may play a role in initiating muscular contractions in the female genitourinary tract.

Hot flashes in postmenopausal women ameliorated by danazol.

Six postmenopausal women with hot flashes were studed for two 8-week periods during which they received low-dose danazol (100 mg/24 hours) for one time interval and placebo for the other in a randomized double-blind manner. The patients recorded the number and severity of their hot flashes daily. On the last day of each period the patients were admitted to the research center overnight for an 8-hour monitoring of forehead skin temperatures and for continuous withdrawal of blood to determine 20-minute integrated levels of luteinizing hormone. Three of the six patients responded to danazol with a mean reduction of 88% in the number of hot flashes and a 53% decrease in the severity of hot flashes. Responders differed from nonresponders in that on treatment the frequency of nocturnal pulses of luteinizing hormone was reduced more (36.1% versus 14.4%), the increase in amplitude of the pulses was greater (+30.7% versus -11.8%), and the fall in the mean level of luteinizing hormone was more marked (19.0% versus 10.5%). The findings suggest that danazol may be a reasonable alternative to estrogen in the treatment of postmenopausal women with severe vasomotor symptoms.

Integrated concentrations of growth hormone, insulin, C-peptide and prolactin in human obesity.

Twenty-four hour integrated concentrations of growth hormone (IC-GH) were significantly lower in young, obese subjects than in young subjects who were lean. Significant inverse correlations were found between IC-GH and body mass index (BMI) as well as the IC-GH and the 24 hr integrated concentrations of insulin (IC-I) and C-peptide (IC-C) in obese subjects below 30 yr of age. Since IC-GH decreases with age, the effect of obesity on IC-GH could not be demonstrated in the older subjects; a weak inverse correlation (p less than 0.05) between IC-GH and IC-C was found. Prolactin was significantly lower in the older subjects but did not correlate with IC-GH and was similar in lean and obese. Lipid deposition in adipose cells is promoted by high concentrations of insulin as well as low concentrations of growth hormone. We found a significant correlation between the IC-I/IC-GH ratio and BMI of both the young and older subjects. Correlations between these two factors do not necessarily imply a cause and effect relationship. It is plausible, however, that the elevated IC-I/IC-GH of the obese may facilitate their lipid storage and counter their efforts at weight reduction.

Autoregulation of rat pituitary prolactin secretion demonstrated by a new perfusion method.

Regulation of prolactin secretion was investigated by perfusing rat pituitaries in vitro. Two pituitary glands from inbred rats were transplanted beneath the renal capsule of a third recipient rat. Three weeks later, the transplanted kidney was removed and perfused in vitro with a defined cell-free medium. Normal renal function was maintained during perfusion, and cell morphology of the transplants remained unchanged as assessed by electron microscopy. Pituitary prolactin content did not change after 120 min of perfusion despite release of approximately 10 micrograms of hormone. Thyrotropin-releasing hormone (10 ng/ml) did not stimulate prolactin release; dopamine (20 ng/ml) rapidly, but transiently inhibited prolactin release; bromocriptine (20 ng/ml) rapidly and persistently inhibited prolactin release; haloperidol (100 ng/ml) blocked the inhibition by dopamine or bromocriptine, but when given alone inhibited prolactin release. Finally, prolactin release was also inhibited by the presence of 100 and 200 ng/ml, but not 50 ng/ml of NIAMDD RP-1 rat prolactin. It is concluded that in vitro perfusion of transplanted rat pituitaries provides a new model for studying the direct effect of agents on the secretion of prolactin from the pituitary and that rat prolactin and/or its metabolites directly inhibit pituitary prolactin secretion.

Regulation of plasma calcium in rats: age-related roles of PTH and calcitonin.

To determine the influence of aging on the relative roles of parathyroid hormone (PTH) and calcitonin in the control of calcium homeostasis during fasting, we assessed changes in plasma calcium in fasted rats following simultaneous removal of the glands that secrete both hormones. Animals ranging in age from 3 to 34.7 wk were thyroparathyroidectomized or sham operated and bled by orbital puncture prior to and 1.5, 3, and 6 h after surgery. After thyroparathyroidectomy (TPTX), plasma calcium fell immediately and progressively in very young rats (3-6 wk old); in young animals (6.5-9.4 wk old), there was a delay of about 1.5 h pceded by a rise, which persisted for at least 3 h. Since the rise and fall in plasma calcium after TPTX are most likely due to calcitonin and PTH deficiencies, respectively, our observations are consistent with the following hypothesis; in the fasting state, the relative importance of calcitonin and PTH in the regulation of plasma calcium varies with age; PTH appears to play the dominant role in young rats; however, during maturation the importance of calcitonin appears to increase progressively.

Multifactorial regulation of prolactin secretion.

The hypothalamus exerts an inhibitory influence on prolactin release from the anterior pituitary. Whether or not peptide hypothalamic prolactin-regulating factors, analogous to those for other pituitary hormones, exist, remains to be confirmed. There is evidence that catecholamines and indolamines directly affect prolactin release. This concept may explain the pathogenesis of galactorrhoea-amenorrhoea and other endocrine diseases produced by hypothalamic-pituitary disorders.

Further studies on the hypercalcemic effect of acute calcitonin deficiency in rats.

Studies were carried out to determine the origin of the immediate increase in plasma calcium following acute calcitonin deficiency in mature rats. Animals were pre-labelled with 45calcium 24 hours and 4 weeks before thyroparathyroidectomy (TPTX) and 1 hour, 24 hours, 2 and 4 weeks before nephrectomy and TPTX and bled serially over the following 3 hours. In each study the final average weight of the rats was over 300 g. Plasma calcium increased after TPTX. In rats labelled with 45calcium 1 and 24 hours previously, the rise was to small to alter the specific activity of calcium although radiocalcium was unchanged. In contrast, in animals pre-labelled with 45calcium 2 and 4 weeks before TPTX, the increase in stable calcium was associated with a parallel increase in radiocalcium. Consequently, the specific activity of plasma calcium did not differ appreciably from that of controls. These findings confirm the theory that in mature unfed rats acute calcitonin deficiency results in an immediate rise in plasma calcium. Since this increase is due mainly to enhanced transport of calcium from deep bone, our observations are in accord with the view that calcitonin decreases plasma calcium primarily by inhibiting calcium transport from "stable" bone.

Effect of ACTH, alpha-MSH, and beta-Lipotropin on calcium and phosphorus metabolism in the rabbit.

Studies were undertaken to investigate the effects of synthetic 1-24 adrenocorticotropin (ACTH), bovine alpha melanocyte-stimulating hormone (alpha-MSH), and ovine beta lipotropin (beta-LPH) on plasma calcium and phosphate in rabbits. Equimolar concentrations of these hormones were infused intravenously in intact and thyroidectomized animals. In addition, ACTH was similarly administered to adrenalectomized rabbits. ACTH, alpha-MSH, and beta-LPH all lowered plasma calcium and raised plasma phosphate. These changes were not prevented by prior thyroidectomy. ACTH was equally effective in inducing hypocalcemia and hyperphosphatemia in the absence of the adrenal glands, while adrenalectomy alone raised plasma calcium. From these findings we have concluded that 1) ACTH, alpha-MSH, and betaLPH affect phosphate as well as calcium metabolism; 2) these hormones do not act by releasing calcitonin; and 3) ACTH exerts its hypocalcemic-hyperphosphatemic effect, at least in part, independently of its trophic action on the adrenal glands.

Evidence for physiological importance of calcitonin in the regulation of plasma calcium in rats.

To determine the physiological importance of calcitonin in the regulation of plasma calcium, studies were carried out in fasting animals to (a) assess the acute effects of thyroparathyroidectomy (TPTX) and thyroidectomy (TX) on plasma and urinary calcium; (b) investigate whether the changes in plasma calcium produced by removal of the glands were dependent on the presence of the kidney; and (c) determine if the effect of TPTX on plasma calcium is affected by age. Except where otherwise indicated, all studies were carried out on fasting male Wistar rats weighing over 300 g. The following observations were made. (a) TPTX and TX caused an increase in plasma calcium in nephrectomized animals. (b) This increase was not dependent on nephrectomy since in intact animals bearing autoparathyroid transplants TX also caused a significant rise in the mean plasma calcium level (0.37 mg/100 ml at 1 1/2 h). (c) Urinary calcium increased twofold in the 3-h period immediately after TX. (d) In unnephrectomized immature (50-g) rats, TPTX caused a progressive decrease in plasma calcium in contrast to old (360-g) rats, where a significant fall observed at 6 h was preceded by an increase in plasma calcium (0.5 mg/100 ml at 1 1/2 h). From these observations we conclude that: (a) calcitonin must play an important physiological role in the regulation of plasma calcium since the termination of its basal secretion caused an immediate but transient increase in plasma calcium in old unfed rats; (b) the relative importance of calcitonin and parathyroid hormone in the acute regulation of plasma calcium is age-related; and (c) the action of parathyroid hormone on bone may be modified by changes in ambient calcitonin concentration.

Effect of calcium deprivation on parathyroid hormone-mediated bone and kidney contributions to the maintenance of plasma calcium in rats.

This study was designed to investigate the roles of bone and kidney in the acute regulation of plasma calcium by parathyroid hormone (PTH) during prolonged calcium deprivation. The effect of PTH was assessed by gland ablation. Animals were thyroparathyroidectomized or sham-operated and their urine was collected for 3 h. Subsequently they were anaesthetized and bled from the abdominal aorta. In rats fed on a low calcium diet, urinary hydroxyproline excretion was enhanced and, unlike animals fed on a normal diet, decreased 3 h after thyroparathyroidectomy (TPTX). In addition TPTX decreased plasma calcium by 0-45 mg/100 ml in normal rats compared with 1-94 mg/100 ml in animals fed on a calcium-deficient diet. Urinary calcium increased by 161 and 12 mug and accounted for 82 and 1-4 % of the fall in plasma calcium in normal and calcium-deprived animals respectively. The corresponding contributions of bone were 18 and 98-6%. These findings support the view that with prolonged calcium deprivation in adult rats, the relative contributions of bone and kidney to the acute regulation of the plasma calcium level by PTH are reversed. As a result, bone rather than kidney becomes the more important organ. At the same time non-PTH-mediated kidney reabsorption of calcium is increased.