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Biomedical subjects

S L Alexander

Publications and source records attributed to S L Alexander.

46 records · Page 3Linked to original sources

Comparison by three different radioimmunoassay systems of the polymorphism of plasma FSH in mares in various reproductive states.

FSH was measured in the pituitary, and in pituitary venous and jugular blood collected at frequent intervals from mares in various reproductive states, using 3 validated and highly specific radioimmunoassay systems based on different antibodies, 'o', 'h' and 'e'. In the pituitary, 4 forms of FSH were found which differed in isoelectric point and relative potency in the 3 assays. In jugular blood, mean FSH concentrations and short-term patterns depended on the assay used and the reproductive state of the mare. In pituitary venous blood, although FSH concentrations were greatly elevated above jugular values, the relationship amongst the 3 assays was similar to that in jugular blood. However, the pulsatility of FSH secretion at oestrus (1-2 pulses per h in 4 of 5 mares) could be observed only in pituitary blood. When the rate of folliculogenesis was slow (acyclicity, oestrus), FSH concentrations measured in assay 'o' were relatively high and showed smaller fluctuations than in assays 'h' and 'e'. By contrast, when folliculogenesis was rapid (transitional phase, dioestrus), FSH tended to be lowest in assay 'o' and pulses had a similar magnitude in all assays. These results suggest that plasma FSH is polymorphic and that changes in the circulating form may have functional importance. Furthermore, since FSH polymorphism affects immunoactivity, the choice of a radioimmunoassay for clinical or research use is difficult without further FSH structure-function studies to determine which form of the hormone should be measured in a given situation.

Animals↗

Measurement of free cortisol and the capacity and association constant of cortisol-binding proteins in plasma of foals and adult horses.

A direct method for measuring the capacity of the high-affinity binding protein, CBG, based on charcoal adsorption, was validated for use in the horse. Several unique aspects of cortisol binding in the horse were observed: (1) CBG content at birth was the lowest of any species studied, (2) CBG concentration increased with age whereas in other species it decreases, (3) the plasma of the new born foal has a binding protein, not reported for other species, which binds as much cortisol as does CBG. Its capacity and affinity are intermediate between albumin and CBG. It may be involved prenatally in increasing dam to fetus transfer of cortisol, and post-natally in buffering the effects of the huge stress-related peripartum release of cortisol.

Aging↗

Spontaneous and stimulated adrenocorticotropin and vasopressin pulsatile secretion in the pituitary venous effluent of the horse.

Plasma ACTH, arginine vasopressin (AVP), and catecholamines were measured at 5-min intervals in the pituitary venous effluent of the unanesthetized horse. Pulses of ACTH and AVP were found to be surprisingly brief (usually of less than 10-min duration) and frequent (averaging between 15-25 min). A highly significant relationship in the changes in concentration of these two hormones was demonstrated (P less than 0.0002) both at rest and after a mild hypoglycemic stimulus. Although there was also a significant correlation (P less than 0.005) between simultaneous plasma ACTH and AVP values the pulse amplitude ratio of AVP to ACTH showed a considerable variation. A rise in cortisol appeared to have a greater suppressive effect on the amplitude of ACTH than AVP pulses. The gradient in hormonal concentration between pituitary effluent and jugular plasma was at times over 50-fold for ACTH, and 500-fold for AVP. A gradient was also found for epinephrine, norepinephrine, and dopamine. A highly significant correlation (P less than 0.005) was demonstrated between changes in norepinephrine, ACTH, and AVP concentrations, but no such relationship could be shown for epinephrine and dopamine. It is concluded that there is a close temporal relationship between changes in ACTH, AVP, and norepinephrine concentrations. Pulses of these hormones are greater in amplitude and more frequent than would have been suspected from sampling peripheral plasma. The variability in the pulse amplitude ratio of ACTH and AVP may suggest that other factors are affecting ACTH secretion. The ability to sample frequently for several hormones and to obtain a marked gradient in hormonal secretion between the pituitary venous effluent and jugular plasma suggest that the horse should provide an excellent animal model in which to study the regulation of hypothalamic and pituitary hormone secretion.

Adrenocorticotropic Hormone↗

Seasonal variation in the feedback of sex steroid hormones on serum LH concentrations in the male horse.

The possibility of seasonal variation in the feedback effect of testosterone or oestradiol was investigated by giving replacement treatment to geldings for 2-3 weeks during breeding and non-breeding seasons. In the non-breeding season, testosterone suppressed LH values (mean +/- s.e.m., ng/ml) in all geldings (before treatment, 7.5 +/- 2.3; final treatment week, 1.8 +/- 0.2; P less than 0.05), whereas early in the breeding season, testosterone caused a prolonged rise in LH (before, 6.8 +/- 2.3; final week, 18.9 +/- 6.4; P less than 0.05). In all testosterone experiments, LH returned to pretreatment levels within 2 weeks after treatment. Oestradiol treatment caused a prolonged increase (P less than 0.05) in LH concentrations (mean +/- s.e.m., ng/ml) in both seasons (breeding: before 5.2 +/- 1.1; final week, 16.2 +/- 4.8; non-breeding before, 10.9, 20.1 +/- 5.2). We conclude that in geldings the feedback effect of testosterone varies with season and, further, that testosterone replacement may be able to restore to geldings the stallion's seasonal pattern of LH secretion. The results suggest that, in male horses, testosterone and possibly oestradiol, are important components in the neuroendocrine pathway controlling seasonal breeding and, moreover, are essential for the generation of a positive signal for LH secretion in the breeding season.

Animals↗

Effect of graded doses of gonadotrophin-releasing hormone on serum LH concentrations in mares in various reproductive states: comparison with endogenously generated LH pulses.

Luteinizing hormone release induced by a range of small (3.3-33 micrograms) and large (300-500 micrograms) i.v. doses of gonadotrophin-releasing hormone (GnRH) was measured in acyclic (n = 4), luteal phase (n = 3) and follicular phase (n = 5) mares and compared with endogenously generated LH pulses in the same reproductive states. Extrapolation from log-linear dose-response curves showed that an LH pulse comparable to an endogenous one would be simulated by i.v. injection of 7.0 (n = 4) and 4.1 (n = 6) micrograms GnRH in luteal and follicular phase mares respectively; a much smaller dose than the 500 micrograms usually given clinically or experimentally. In acyclic mares (n = 4), LH pulses occurred too infrequently to be characterized. At small doses of GnRH the amount of LH released by the same dose was similar in all three reproductive states, although the steroid hormone milieu differed markedly. This implies that observed differences between states in mean (+/- S.E.M.) serum LH concentrations (0.7 +/- 0.01, 1.2 +/- 0.03 and 11.6 +/- 0.33 (microgram/l) in acyclic, luteal and follicular phase mares respectively) were produced by differences in GnRH pulse frequency and/or amplitude and not by steroid-mediated changes in pituitary response to GnRH. In acyclic, luteal and follicular phase mares, LH pulse frequency was: immeasurably low, 0.09 and 1.14 pulses/h respectively, which supports the important contribution of pulse frequency to determining mean LH concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sexual behavior and serum concentrations of reproductive hormones in normal stallions.

Recently, it has been reported that impotence in the stallion has a physiological basis that involves decreased serum concentrations of luteinizing hormone (LH) and estradiol-17beta, but not testosterone. We have found such a hormonal profile in two of nine stallions studied during an ongoing investigation of the endocrinology of the normal stallion. Nevertheless, both of these stallions possessed vigorous libido and normal seminal characteristics. We conclude that the hormonal profile of low LH, low estradiol and normal testosterone, although it may accompany impotence in the stallion, is not predictive of, or causally related to, abnormalities in sexual behavior.

Journal Article↗

Coronary blood flow and distribution in right ventricular hypertrophy.

Myocardial blood flow and distribution in animals with righ ventricular (RV) hypertrophy have not been studied extensively in the experimental laboratory. This study was carried out to investigate whether or not ischemia can be induced in the hypertrophied right ventricle. Ten adult foxhounds underwent banding of the pulmonary artery. One year later coronary flow and distribution were studied by use of radioactive microspheres. Myocardial oxygen supply and demand were estimated by planimetry of aortic and RV pressure tracings. Data were obtained in the control state, during atrial pacing to a heart rate of 200 +/- 4 beats/min (mean +/- SD), during aorta-right atrial shunting to reduce mean aortic pressure to 60 +/- 6mm Hg, and during aortic constriction to produce a mean aortic pressure of 145 +/- 8mm Hg. RV weight/body weight ratio was 2.2 +/- 0.2 gm/kg(normal, 1.3 +/- 0.1 gm/kg) (p less than 0.001). RV free wall thickness was 11.3 +2- 0.7 mm (normal, 6.7 +/- 0.4 mm) (p less than 0.001). At rest, RV oxygen supply/demand ration was 4.7, and the RV subendocardial/subepicardial (Endo/Epi) flow ratio was 0.93. During atrial pacing, RV supply/demand was 54% of control (p less than 0.01), RV Endo/Epi ratio was 1.00 (p less than 0.05), and right coronary artery (RCA) resistance was 59% of control (p less than 0.01). Aorto-right atrial shunting resulted in an RV supply/demand ratio of 31% of control (p less than 0.01), RV Endo/Epi ratio of 0.95, and RCA resistance of 45% of control (p less than 0.01). During aortic constriction, RV supply/demand ratio was 132% of control (p less than 0.05), RV Endo/Epi ratio was 0.92, and RCA resistance was 146% of control (p less than 0.01). Phasic RCA flowmeter tracings demonstrated an increased proportion of diastolic flow in the study animals as compared to normal animals. In conclusion, myocardial blood flow and distribution in the hypertrophied right ventricle remained normal at rest and during hemodynamic stress. Compensatory mechanisms which maintain normal flow and distribution may include changes in RCA resistance and phasic flow patterns. Under the imposed conditions, RV ischemia and failure did not occur.

Animals↗