Prenatal screening for hemoglobinopathies. III. Applicability of the health belief model.

A comprehensive prenatal hemoglobinopathy screening program in Rochester, NY, has been described in a preceding paper in this issue of the Journal. A woman identified as a carrier may face three decisions. The first is whether to accept the offer of counseling. The second is whether to have her partner tested. If her partner also tests positive, then the third decision is whether to accept the offer of prenatal diagnosis. This report analyzes factors affecting her decision, with special attention being given to factors invoked by the Health Belief Model. Factors predicting that a patient who we identified as a carrier would come for counseling included the following: patient had no prior knowledge that she is a carrier (P less than .001), a gestational age less than 18 wk (P less than .01), and Caucasian race (P less than .05). For sickle cell trait counselees and beta-thalassamia trait counselees, factors found to predict patient's intent to have partner tested were the following: a greater postcounseling knowledge of the disease (P less than .009), a lesser perceived burden of intervention (P less than .011), and belief that the partner is also a carrier (P less than .008). Also for sickle cell trait counselees and beta-thalassemia trait counselees, factors predicting that the partner actually will be tested were the following: living with the partner (P less than .001), gestational age at identification less than or equal to 18 wk (P less than .001), a lesser perceived burden of intervention (P less than .002), and a greater perceived seriousness of the disease (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The permeability of rat liver lysosomes to sugars. Evidence for carrier-mediated facilitated diffusion.

1. By the osmotic-protection method, the penetration of sugars through the rat liver lysosomal membranes was studied with a view of determining whether sugar uptake was by facilitated diffusion. 2. The following criteria for this type of transport were established: sugar specificity, the order of uptake being 2-deoxy-D-glucose less than D-glucose less than D-mannose less than D-galactose less than D-ribose less than 2-deoxy-D-ribose; stereospecificity, the uptake of L-glucose and L-ribose being 50% slower than their D-stereoisomers; inhibition by 1 MM-phlorrhizin and 1 M-cytochalastin B; competition between sugars for uptake, and a Q10 (rate difference over a 10 degrees C temperature range) for uptake of approx. 2.8. 3. It is proposed that sugar uptake into lysosomes from rat liver is by facilitated diffusion.     

Evaluation of flurbiprofen in detrusor instability.

Thirty women with detrusor instability (27 cases idiopathic, and three secondary to multiple sclerosis) completed a double-blind, cross-over trial of the prostaglandin synthetase inhibitor flurbiprofen and a placebo, results being evaluated by questionnaire and cystometry. Frequency, urgency, and urge incontinence were all significantly reduced with flurbiprofen (P less than 0.001, P less than 0.025, and P less than 0.025 respectively), as was the detrusor-pressure rise during bladder filling (P less than 0.01). Side effects, however, occurred in 13 patients while taking flurbiprofen compared with five while taking placebo (P less than 0.025). After the trial 19 patients wished to continue with flurbiprofen. Flurbiprofen is a useful treatment for idiopathic detrusor instability and is well tolerated by most patients.     

New anthracycline antibiotics produced by interspecific recombinants of streptomycetes. IV. Antimicrobial activity of iremycin

The in vitro antimicrobial activity of iremycin (10-(alpha-L-rhodosaminyl)-gamma-rhodomycinone) was determined in comparison to that of doxorubicin, a 14-hydroxy-derivative of daunorubicin, which exhibited a strong antitumor activity and is useful in chemotherapy of human tumors. The MIC values determined by means of a standardized agar diffusion plate test indicated a lower antimicrobial activity of iremycin in vitro in comparison to that of doxorubicin. In contrast to doxorubicin, iremycin was highly active against Mycobacterium smegmatis, but five-fold less active than doxorubicin against Staphylococcus aureus, seven-fold less active against Bacillus subtilis, and twenty five-fold less active against Commamonas terrigena. Furthermore, iremycin was hundred-fold less active against a highly sensitive permeation mutant of Pseudomonas aeruginosa. No inducing activity on prophages in lysogenic E. coli cells was demonstrable for iremycin and no growth inhibition in the repair test was observable. In contrast, iremycin inhibited the multiplication of gamma-phages in the BIP test, but the MIC values of violamycin BI, doxorubicin and iremycin in this test system indicated that iremycin is two hundred fifty-fold less active than violamycin BI and ten-fold less active than doxorubicin. No serum binding was demonstrable for iremycin.     

Prediction of beta-turns.

An automated computer prediction of the chain reversal regions of globular proteins is described herein using bend frequencies and beta-turn conformational parameters (Pt) determined from 408 beta-turns in 29 proteins calculated from x-ray atomic coordinates. The probability of bend occurrence at residue i is pt = fi X fi+1 X fi+2 X fi+3 with the average bend probability less than Pt greater than = 0.55 X 10(-4). Tetrapeptides with pt greater than 0.75 X 10(-4) ( approximately to 1.5 X less than pt greater than) as well as less than Pt greater than 1.00 and less than Pa greater than less than less than Pt greater than greater than less than P beta greater than are selected by the computer as probable bends. Adjacent probable bends (i.e., 11-14, 12-15, 13-16) are compared pairwise by the computer, and the tetrapeptide with the higher pt value is predicted as a beta-turn. The percentage of bend and nonbend residues predicted correctly for 29 proteins by this computer algorithm is %t+nt = 70%, whereas 78% of the beta-turns were localized correctly within +/- 2 residues. The average beta-turn content in the 29 proteins is 32%, with helical proteins having fewer bends (17%) than beta-sheet proteins (41%). Three proteins having iron-sulfur clusters were found with the highest percentages of beta-turns: Chromatium high potential iron protein (65%), ferredoxin (57%), and rubredoxin (65%). Finally, the bend frequencies at all 12 positions from 457 beta-turns in 29 proteins (Chou and Fasman, 1977) were used to test the effectiveness of predicting bends using 2, 4, 8, and 12 residues as well as different cut-off pt values. The computer analysis showed that 1.25 less than pt greater than to be the best cut-off yielding 70% accuracy in %t+nt for 4 residues and %t+nt = 73% for 12 residues in predicting the bend and nonbend regions of proteins.     

The dimerization of ferrihaems. I. The effect of buffer ions and specific cations on deuteroferrihaem dimerization.

The dimerization of dueteroferrihaem in aqueous solution has been investigated using a parameter, named the dimerization index (Robs). This is defined as the ratio of extinction coefficients at wavelengths corresponding to Soret band maxima for the monomeric and dimeric species, respectively. For solutions containing mainly monomeric species, Robs greater than 2, whereas for solutions containing mainly dimeric species Robs less than 1. A computer programme has been applied to determine values of the dimerization constant, K, defined as: K = [dimer] [H+]/[monomer]2. Phosphate buffer anions and Tris . HCl buffer enhanced dimerization. Monovalent and divalent cations also increased dimerization, but in a specific manner. The magnitudes of their effects increased in the order K+ less than Na+ less than Li+ less than Sr2+ less than Mg2+ approximately or equal to Ca2+. Values of K were determined for several concentrations of Na+ and Sr2+. These data are interpreted in terms of a stabilization of the ferrihaem dimer by the formation of ion triplets with the added cation 'sandwiched' between carboxyl residues of the adjacent ferrihaem monomeric units. General guidelines are recommended for the choice of conditions which minimize dimerization.     

Opiate properties of SKF 525A.

SKF 525A, a classical inhibitor of microsomal drug-metabolizing enzymes, is structurally similar to the diphenylpropylamine analgesics, and certain reported effects in animals resemble those produced by opiate drugs. In an opiate radioreceptor assay, SKF 525A was 50 times less potent than methadone in the absence of sodium and 10 times less potent in the prescence of sodium. The nature of the sodium effect indicates SKF 525A to have less opiate agonist character than does methadone. In mice, 2 mg of SKF 525A given intraperitoneally induced less profound analgesia on a hot plate (44 degrees C) than did 0.1 mg of methadone. Analgesia by SKF 525A was prevented by pretreatment of the mice with naloxone. In rats, 50 microgram of SKF 525A given intracerebroventricularly was analgesic.     

Orientation of male Heterodera rostochiensis Woll. and H. schachtii Schm. to their females

A chemical attractive to their males is emitted by females of Heterodera rostochiensis and H. schachtii. The attraction is evident in agar plates when the females have been killed or removed from the agar, and on 3 mm. thick agar it takes more than 15 min. at 20° C. to diffuse sufficiently to be perceptible to males 5 mm. from the females. The perception is gustatory and seems to elicit klinokinetic aggregation behaviour and klinotaxic orientation. The males respond to a decrease in stimulation by stopping, followed by either a reversal and turn, or a swing and turn. Fatigue of the receptors, leading to loss of acuity of perception, occurs at greater concentrations of the attractant and decreases the frequency of turning. Then the intensity of turning increases and the approach to the female is less well orientated. Females of H. schachtii secreted a less labile or more concentrated attractant; thus their males were more frequently less well orientated and removal of the females caused more direct attraction. Male behaviour was efficient enough to ensure mating even of isolated females.     

Case--control study of counselling against neonatal circumcision.

After two serious complications had alerted physicians to the potential risks of routine neonatal circumcision, the circumcision rate in a regional general hospital decreased significantly (p less than 0.001), from approximately 40% to 20%, settling at the level claimed to prevail when physicians oppose circumcision. Following this decrease 219 consecutive pregnancies resulting in male infants were prospectively studied in order to identify factors associated with insistence on circumcision. Factors significantly associated with circumcision were the existence of an older brother (p less than 0.001), especially if circumcised (p less than 0.001), and delivery of prenatal care by an obstetrician rather than a general practitioner (p less than 0.05). Factors significantly associated with no circumcision were the fact that this infant was the first male born in the family (p = 0.001), delivery of prenatal and infant care by the same general practitioner (p less than 0.05) and a maternal age of 20 years or less (p less than 0.02). The circumcision status of the father, the marital status of the mother, the mother''s intention to breast-feed, attendance of a primigravida at prenatal classes, delivery of infant care by a pediatrician and socioeconomic status did not appear to influence whether circumcision was performed. These data may assist physicians in understanding the potential effectiveness and limitations of counselling against circumcision.     

Effect of sex steroids on body temperature in postmenopausal women. Role of endogenous opioids.

The role of endogenous opioids on the thermoregulatory effect of sex steroids was investigated in six postmenopausal women before and during treatment with transdermal 17 B-estradiol (TTS 50; 50 mcg/day) with or without vaginal progesterone (P4; 100 mg twice daily). In all the different endocrine conditions, saline or the opioid antagonist naloxone (10 mg/hr. preceded by 10 mg iv bolus) were randomly infused for 4 hrs., on two consecutive days. Measurements of body temperature (BT) variations were performed by a thermistor probe placed in the rectum. BT did not significantly vary from baseline values during saline infusion, whereas it significantly decreased during the infusion of naloxone performed, either before treatment (p less than 0.01), during TTS 50 administration (p less than 0.01), or during TTS 50 + P4 (p less than 0.025). The naloxone induced decrease of BT was greater during TTS 50 administration than before treatment (p less than 0.025). The addition of P4 to TTS 50 administration increased baseline BT of 0.4 degrees C (p less than 0.01), and reduced the ability of naloxone to reduce BT (p less than 0.01 vs. TTS 50). The hyperthermic effect of P4 was not abolished by the infusion of naloxone. Our data show that in postmenopausal women the effect of endogenous opioid peptides on BT is enhanced by estradiol and reduced by progesterone. The hyperthermic effect of progesterone does not seem to be mediated by an increased endogenous opioid activity.     

Transient analysis of cardiopulmonary interactions. II. Systolic events

The etiology of the fall in left ventricular stroke volume (LVSV) and arterial pressure with a negative intrathoracic pressure (NITP) during inspiration is controversial. An increase in LV afterload produced by NITP has been proposed as one explanation but is difficult to evaluate if preload is also altered. To test the hypothesis that a systolic event alone, i.e., a change in LV afterload or contractility, can reduce LVSV during inspiration independent of changes in LV preload, a rapid transient NITP confined to systole was produced by electrocardiogram-triggered phrenic nerve stimulation in eight anesthetized dogs. Intrathoracic descending aortic diameters were measured by sonomicrometry to transduce qualitative changes in aortic transmural pressure. With the airway completely obstructed systolic NITP resulted in a decrease in LVSV (-8.1%, P less than 0.001) but an increase in the systolic anteroposterior (0.54 mm, P less than 0.01) and right-to-left (0.45 mm, P less than 0.01) aortic diameters compared with preceding beat. Similar significant changes were observed with the airway unobstructed. These observations are consistent with an increased afterload imposed on the LV reducing LVSV and egress of blood out of the thorax. Prolonging NITP to include both systole and diastole, a profound fall in LVSV is observed, consistent with the independent influences of systolic and diastolic events combining to diminish LVSV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anion permeation in the proximal tubule of Necturus kidney: the shunt pathway.

The effect of foreign anions on transepithelial potential difference and transepithelial input conductance was studied in the isolated perfused Necturus kidney. Two microelectrodes (recording and current-injecting) were inserted into the lumen of single proximal tubules and the peritubular perfusate was shifted reversibly for 30-60 sec from a physiologic Ringer's solution to a test solution in which chloride was replaced isosmotically by a foreign anion. The permeability sequence, obtained by potential measurements, was: lactate less than glutamate less than gluconate less than pyruvate less than benzene sulfonate less than or equal to acetate less than or equal to F less than propionate less than BrO3 less than formate less than ClO3 less than Cl than ClO4 less than I less than or equal to Br less than NO3 less than SCN. Transepithelial conductance decreased when the tissue was perfused with anions less permeable than chloride but the conductance sequence was different from the permeability sequence. Such discrepancies were more pronounced during perfusion with hyperpolarizing anions; ClO4 and I- (both more permeable than chloride) produced an important decrease in transepithelial conductance, followed by incomplete reversibility when the perfusion was shifted again to chloride Ringer's. The results are best explained by the presence of weak positive fixed charges, governing anion permeation, at the shunt pathway of the proximal tubule. An analysis of the data allows tentative estimates of shape and size of the sites.     

Enzymatic analysis of isomeric trithymidylates containing ultraviolet light-induced cyclobutane pyrimidine dimers. I. Nuclease P1-mediated hydrolysis of the intradimer phosphodiester linkage

Our recent findings suggest that enzymatic hydrolysis of the intradimer phosphodiester bond may constitute the initial step in the repair of UV light-induced cyclobutane pyrimidine dimers in human cells. To examine the susceptibility of this phosphodiester linkage to enzyme-mediated hydrolysis, the trinucleotide d-Tp-TpT was UV-irradiated and the two isomeric compounds containing a cis-syn-cyclobutane dimer were isolated by high performance liquid chromatography and treated with various deoxyribonucleases. Snake venom phosphodiesterase hydrolyzed only the 3'-phosphodiester group in the 5'-isomer (d-T less than p greater than TpT) but was totally inactive toward the 3'-isomer (d-TpT less than p greater than T). In contrast, calf spleen phosphodiesterase only operated on the 3'-isomer by cleaving the 5'-internucleotide bond. Kinetic analysis revealed that (i) the activity of snake venom phosphodiesterase was unaffected by a dimer 5' to a phosphodiester linkage, (ii) the action of calf spleen phosphodiesterase was partially inhibited by a dimer 3' to a phosphodiester bond, and (iii) Escherichia coli phr B-encoded DNA photolyase reacted twice as fast with d-T less than p greater than TpT as with d-TpT less than p greater than T. Mung bean nuclease, nuclease S1, and nuclease P1 all cleaved the 5'-internucleotide linkage, but not the intradimer phosphodiester bond, in d-TpT less than p greater than T. Both phosphate groups in d-T less than p greater than TpT were refractory to mung bean nuclease or nuclease S1. Incubation of d-T less than p greater than TpT with nuclease P1, however, generated the novel compound dT less than greater than d-pTpT containing a severed intradimer phosphodiester linkage. Accordingly, nuclease P1 represents the first purified enzyme known to hydrolyze an intradimer phosphodiester linkage.     

Fate of bradykinin-potentiating peptide 9a after intravenous injection.

The fat of less than Glu1-3H-labelled bradykinin-potentiating peptide 9a [BPP9a; less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, an inhibitor of angiotensin-converting enzyme (peptidyl dipeptidase)] was studied in the rabbit. After intravenous injection, BPP9a was rapidly removed from blood and much of the associated radioactivity was excreted in urine. Approx. 8% of the radioactivity in urine collected 2h after drug administration occurred in the form of BPP9a itself, the remainder occurring in three lower homologues: less than Glu-Trp (60%), less Glu-Trp-Pro-Arg-Pro-Gln (20%) and less than Glu-Trp-Pro-Arg-Pro-Gln-Ile (12%). Hydrolysis was not accounted for by enzymes in blood or urine. Apparently hydrolysis occurred within the kidney, as less than Gl-Trp was obtained in 60% yield in urine of isolated rat kidney perfused with [less than Glu1-3H]BPP9a.     

Biological growth and spread modeled by systems of recursions. I. Mathematical theory

We study the asymptotic behavior of solutions to a system of recursions u in+1 = Qi[mu n], i = 1, ..., k. The vector operator Q has the origin theta and a positive vector beta as fixed points and is defined for vector-valued functions bounded between theta and gamma where gamma greater than or equal to beta. In addition, Q is order-preserving, commutes with translation, and is continuous in the topology of uniform convergence on compact subsets. Let theta less than or equal to pi much less than beta, and suppose that for all pi much less than alpha much less than beta, Q(n) alpha]----beta as n----infinity. If u0 much greater than pi on a sufficiently large ball and has bounded support, then un propagates with a speed c*(xi) in the direction of the unit vector xi as n----infinity. In certain cases, c*(xi) can be calculated explicitly. The results generalize those of a scalar equation studied by Weinberger.     

Glucose regulation of guinea-pig sperm motility.

Washed guinea-pig spermatozoa from the vas deferens re-acquired progressive motility within 1-2 min of incubation in minimal culture medium containing pyruvate and lactate. When glucose was added, either at the beginning or after 15 min of incubation, the cells showed stimulated motility (increased straight-line velocity, linearity and beat-cross frequency, P less than 0.01). Re-acquisition of progressive motility was preceded by a significant (P less than 0.005) transient increase in sperm concentration of cyclic adenosine 5'-phosphate (cAMP) with or without glucose in the medium. Papaverine caused another large significant (P less than 0.001) increase in cAMP concentration; and 5.56mM glucose with papaverine caused a further stimulation in cAMP beyond that with papaverine alone (P less than 0.005). Although 0.05 or 5.56mM glucose plus alpha-chlorohydrin stimulated sperm motility, they did not further stimulate the increase in cAMP after 30 s of incubation. Thus, there was no apparent correlation between the glucose-stimulating effect on sperm motility and the enhancement of cAMP at 30 s. However, there was a close correlation between glucose-stimulated motility and enhancement of ATP (P less than 0.05) by glucose even under incubation conditions in which glucose caused the Crabtree effect (decrease in respiration rate).     

Temporary network formation of hyaluronate under a physiological condition. 1. Molecular-weight dependence

The dynamic shear moduli at various frequencies and stress growth after the sudden start of steady shear were measured for 1% HA (hyaluronic acid) solutions with different molecular weights. From the results of the zero shear viscosity, eta 0, the steady shear compliance, J 0e, and delta eta defined as delta eta = eta 0 - eta a (infinity), where eta a (infinity) is the apparent viscosity at the steady state, it was shown that the molecular mechanism of flow of 1% HA solutions was classified into four regions with respect to molecular weight: (I) the viscosity-average molecular weight Mv less than 35 X 10(4), HA chains are dispersed molecularly in solution; (II) 35 X 10(4) less than Mv less than 100 X 10(4), the polymer chains form a weak entanglement network observed only through eta 0; (III) 100 X 10(4) less than Mv less than 160 X 10(4), the network is strengthened with increasing molecular weight and becomes detectable through both eta 0 and J 0e and also through the overshoot phenomenon; and (IV) 160 X 10(4) less than Mv, the network is "saturated" or "completed" dynamically. This is the conjecture presented for the first time by the present work.     

2 new species of parasites of fish, Myxobilatus schulmani sp. n. and Apiosoma longiciliaris sp. n. of the water reservoirs of the Kol'sk peninsula]

Two new species of parasitic Protozoa are described, one of Myxosporidia and the other of Peritricha Sessilia. Myxobilatus schulmani sp. n. from Pungitius pungitius is near to M. paragasterostei but differs from it by the rhombus form of the spore, by less dimension of polar capsules. The spore of M. shulmani is longer and less broader than that of M. paragasterostei. Apiosoma longiciliaris sp. n. was found on the gills on Esox lucius and Phoxinus phoxinus. It is near to A. dallii but its micronucleus is situated over the macronucleus and has a stick like form.     

Protease priming of neutrophil superoxide production. Effects on membrane lipid order and lateral mobility.

Phagocyte superoxide (O2-) response is primed by a variety of physiologic compounds including the neutrophil secretory proteases cathepsin G and elastase. To study whether protease priming of neutrophil O2- response is related to changes in membrane physical state, we examined enzyme effects on the order and lateral mobility of lipid probes in intact neutrophil membranes. Exposure to cathepsin G (5 micrograms/ml) or elastase (10 micrograms/ml) caused a significant decrease in fluorescence anisotropy of the probe trimethylammonium diphenylhexatriene in neutrophil plasma membranes (0.279 to 0.256 for cathepsin G, 0.274 to 0.256 for elastase, p less than 0.02 for both), indicating a decrease in phospholipid chain order in the surface membrane bilayer. Cathepsin G and elastase also caused significant increases in membrane lipid lateral mobility as measured by excimer formation of the fluorescent probe 1-pyrenedecanoic acid (for cathepsin G, a 107% increase, and for elastase, a 44% increase in excimer/monomer fluorescence ratio, p less than 0.001). Enzyme effects on membrane structure were dependent on intact proteolytic activity, and were cell specific; the proteases had no effect on lipid order or lateral mobility in liposomes. In corollary studies, the possible association between the physical state of the polymorphonuclear leukocyte membrane and O2- generation was analyzed with the membrane modifying compounds, linoleic acid, ethanol, and cholesterol. Cell exposure to linoleic acid (1 microM) caused a significant decrease in lipid order and an increase in lipid lateral mobility along with increased O2- production to N-formyl-Met-Leu-Phe (fMLP) (191%) and phorbol myristate acetate (PMA) (39%), p less than 0.02 for each. 3 mM ethanol also augmented O2- response to fMLP (31%) and PMA (48%) and caused a significant decrease in lipid order, but did not affect lipid lateral mobility. Treatment with cholesteryl hemisuccinate (100 micrograms/ml) resulted in increased lipid order and decreased lipid lateral mobility, as well as decreased neutrophil superoxide response to fMLP (-61%, p less than 0.001) and PMA (-50%, p less than 0.02). We then examined whether modulation of membrane physical state may explain the mechanism of action of a known priming agent by studying the effects of low concentrations of a diacylglycerol. Cells treated with 10 microM 1-oleoyl-2-acetyl-sn-glycerol had a greater than 8-fold increase in superoxide response to fMLP (p less than 0.001) while demonstrating a significant decrease in lipid order (0.289 to 0.281, p less than 0.01) and a 50% increase in lipid lateral mobility (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)     

Gonadotrope responsiveness in orchidectomized sheep: I. Effect of continuous infusion of estradiol.

Gonadotrope function during continuous infusion of estradiol (E2) was evaluated in orchidectomized sheep (wethers). Serum concentrations of LH were reduced (p less than 0.05) within 3 h of introduction of E2 and remained depressed for the period of E2 delivery (48 h). Gonadotrope responsiveness (change in LH secretion induced by a 500-ng GnRH challenge, i.v.) was assessed 0, 3, 6, 12, 24, or 48 h after initiation of E2 infusion. Gonadotrope responsiveness was augmented (p less than 0.05) 12, 24, and 48 h after first introduction of E2. In a companion study, anterior pituitary tissue was collected 0, 3, 6, 12, 24, or 48 h after the beginning of E2 infusion. Tissue concentration of GnRH receptor was increased 3-fold within 12 h of first introduction of E2. Tissue stores of LH were also increased (p less than 0.05) during E2 infusion. Passive immunization against GnRH increased (p less than 0.05) tissue stores of LH, but had no effect on GnRH receptor concentration. Passive immunization against GnRH and concurrent infusion of E2 increased (p less than 0.05) both tissue stores of LH and tissue concentrations of GnRH receptor. The acute suppression of LH secretion induced by infusion of E2 was not affected by concurrent episodic administration of GnRH (200 ng/hourly pulse). However, serum concentrations of LH were restored to pretreatment levels within 12 h of initiation of E2 infusion and episodic delivery of GnRH. These data indicate that E2 acts in wethers to suppress gonadotropin secretion while simultaneously increasing GnRH receptor concentration, tissue stores of LH, and gonadotrope responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)