The temporal interaction of corticosterone and prolactin in affecting liver lipid metabolism of the chick

Experiments were conducted to determine if Brown Leghorn chickens (Gallus domesticus) showed a daily differential responsiveness to the phased injections of corticosterone and prolactin. In experiment 1, 28 day old chicks, maintained on continuous lighting and a standard diet, were treated daily for 6 days with corticosterone (300 mug. in 0.2 cc. saline) and with prolactin (150 mug. in 0.2 cc. saline) for 4 days. The prolactin injections began 2 days after the first corticosterone injection. The interval between daily corticosterone injections at 1800 hours followed by prolactin injections 6, 12 or 18 hours later resulted in a significant increase in the liver lipidcontent in the chicks. However, when corticosterone and prolactin were given at the same time (1800 hours), no increase in liver lipid content was observed. Corticosterone admininstered at 6oo hours and followed by prolactin injections had no effect on liver lipid content regardless of the time of prolactin prolactin injections. Experiment 2 was designed to test the effect of the administration of corticosterone or prolactin alone at either 600 hours or 1800 hours on liver lipid metabolism. Two groups of Brown Leghorn chicks received prolactin alone (for 2 days) at either 600 hours or 1800 hours. None of these treatment groups were significantly different from the uninjected controls. It is concluded that the chick has a diurnal sensitivity to the effects of coritcosterone and that once the liver is affected by corticosterone, a temporal interaction between this steroid and prolactin can affect the liver lipid content of the Brown Leghorn chick.     

Hemodynamic determinants of the time-course of fall in canine left ventricular pressure

The hemodynamic determinants of the time-course of fall in isovolumic left ventricular pressure were assessed in isolated canine left ventricular preparations. Pressure fall was studied in isovolumic beats or during prolonged isovolumic diastole after ejection. Pressure fall was studied in isovolumic relaxation for isovolumic and ejecting beats (r less than or equal to 0.98) and was therefore characterized by a time constant, T. Higher heart rates shortened T slightly from 52.6 +/- 4.5 ms at 110/min to 48.2 +/- 6.0 ms at 160/min (P less than 0.01, n = 8). Higher ventricular volumes under isovolumic conditions resulted in higher peak left ventricular pressure but no significant change in T. T did shorten from 67.1 +/- 5.0 ms in isovolumic beats to 45.8 +/- 2.9 ms in the ejecting beats (P less than 0.001, n = 14). In the ejecting beats, peak systolic pressure was lower, and end-systolic volume smaller. To differentiate the effects of systolic shortening during ejection from those of lower systolic pressure and smaller end-systolic volume, beats with large end-diastolic volumes were compared to beats with smaller end-diastolic volumes. The beats with smaller end-diastolic volumes exhibited less shortening but similar end-systolic volumes and peak systolic pressure. T again shortened to a greater extent in the beats with greater systolic shortening. Calcium chloride and acetylstrophanthidin resulted in no significant change in T, but norepinephrine, which accelerates active relaxation, resulted in a significant shortening of T (65.6 +/- 13.4 vs. 46.3 +/- 7.0 ms, P less than 0.02). During recovery from ischemia, T increased significantly from 59.3 +/- 9.6 to 76.8 +/- 13.1 ms when compared with the preischemic control beat (P less than 0.05). Thus, the present studies show that the time-course of isovolumic pressure fall subsequent to maximum negative dP/dt is exponential, independent of systolic stress and end-systolic fiber length, and minimally dependent on heart rate. T may be an index of the activity of the active cardiac relaxing system and appears dependent on systolic fiber shortening.     

Skeletal resistance to the calcemic action of parathyroid hormone in uremia: role of 1,25 (OH)2 D3

Studies were carried out to investigate the role of 1,25(OH)2D3 in the skeletal resistance to the calcemic action of parathyroid hormone. The change in serum calcium after the intravenous infusion of 2 U of parathyroid extract (PTE)/kg body wt/hr for eight hours was evaluated in thyroparathyroidectomized (T-PTX) dogs before, and one, two and three days after, induction of uremia by bilateral ureteral ligation (11 dogs) or by bilateral nephrectomy (8 dogs). In another six nephrectomized and T-PTX dogs, 0.68 ug of 1, 25 (OH)2D3/day was given on the day of nephrectomy and for two days thereafter. Serum creatinine in each day of the study was not different among the three groups. The study also included the evaluation of the effect of sham operation (five dogs) and the administration of 1,25 (OH)2D3 to dogs with normal renal function (four dogs) on the calcemic response to PTE, as well as the reproducibility of such a response in the same animal. The results showed that 1) the calcemic response to PTE was markedly impaired after one day of bilateral ureteral ligation or nephrectomy, but the impairment was more severe after nephrectomy; 2) the calcemic response to PTE after two or three days of bilateral ureteral ligation was similar to that seen at one day after nephrectomy; 3) 1, 25 (OH)2D3 partially restored the calcemic response to PTE in the nephrectomized animals to levels similar to those seen after one day of bilateral ureteral ligation; 4) sham operation did not affect the response to PTE, and repeated infusion of PTE produced similar changes in the concentrations of serum calcium. The data indicate that (a) a deficiency of 1,25 (OH)2D3 is at least partly responsible for the skeletal resistance to the calcemic action of PTH in uremia; (b) uremia, per se, may also contribute to this phenomenon; and (c) the kidney after one day of complete bilateral ureteral ligation may still produce 1,25 (OH)2D3, but this ability is compromised after two days of ureteral obstruction.     

A reappraisal of the stereoselective metabolism of nicotine to nicotine-1'-N-oxide

1. The cis and trans 1'-N-oxide metabolites of (2'R)-(+)-nicotine have the absolute configuration (1'S; 2'R) and (1'R; 2'R), respectively, and not the reverse as previously published. 2. Reinterpretation of metabolic data in the light of this reassignment reveals that N-oxidation of nicotine leads preferentially to the (1'R)-N-oxide, with little dependence on the configuration of the 2'-centre. 3. It is proposed that (2'S)-(-)-nicotine and (2'R)-(+)-nicotine bind to the same enzymic site by two distinct modes of binding; each of these modes involves the more basic centre (in this case the pyrrolidine ring) as the governing binding moiety.     

Endocrine studies during the refeeding of young women with nutritional amenorrhea and infertility

Serial endocrine studies were performed during the refeeding of a group of nine young women who presented with amenorrhea associated with injudicious dieting. No significant psychopathology was disclosed by the Lanyon Psychological Screening Inventory in any of the patients, six of whom were single and three married and infertile. The mean weight before refeeding was 81.6% of the normal for height. The mean initial serum follicle-stimulating hormone concentration was within the limits of normal for young women of reproductive age, but the serum luteinizing hormone (LH) concentration and the vaginal maturation score were low. As weight was regained, the serum LH concentration increased (the pooled r for LH versus percent normal weight = 0.85) and the vaginal maturation score rose (the pooled r for vaginal maturation score versus percent normal weight = 0.93). When a mean weight of 96.6% of normal was reached after a mean of 5.3 (range, 2 to 11) months of refeeding, spontaneous menses occurred. The initial cycle was ovulatory in two instances and anovulatory in five, as determined by basal body temperature patterns, plasma progesterone concentrations, and endometrial biopsies. With continued weight gain, menstruation became regular and the three married patients conceived.