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E R Hauser

Publications and source records attributed to E R Hauser.

At least 37 records · Page 2Linked to original sources

Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group.

Large-scale genotyping is required to generate dense identity-by-descent maps to map genes for human complex disease. In some studies the number of genotypes needed can approach or even exceed 1 million. Generally, linkage and linkage disequilibrium analyses depend on clear allele identification and subsequent allele frequency estimation. Accurate grouping or categorization of each allele in the sample (allele calling or binning) is therefore an absolute requirement. Hence, a genotyping system that can reliably achieve this is necessary. In the case of affected sib-pair analysis without parents, the need for accurate allele calling is even more critical. We describe methods that permit precise sizing of alleles across multiple gels using the fluorescence-based, Applied Biosystems (ABI) genotyping technology and discuss ways to reduce genotyping error rates. Using database utilities, we show how to minimize intergel allele size variation, to combine data effectively from different models of ABI sequencing machines, and automatically bin alleles. The final data can then be converted into a format ready for analysis by statistical genetic packages such as MENDEL.

Alleles↗

Affected-sib-pair interval mapping and exclusion for complex genetic traits: sampling considerations.

We describe an extension of Risch's [(1990a,b) Am J Hum Genet 46:222-228, 229-241] method of linkage detection and exclusion for complex genetic traits. The method uses interval mapping to infer disease locus identity-by-descent (IBD) sharing for affected sib pairs (ASPs) based on marker information for the ASP and other genotyped family members. The method is likelihood based, and makes use of Risch's parameterization in terms of recurrence risk ratios for relatives. We describe specific linkage detection and exclusion tests for use as genome screening tools to prioritize genomic regions for further study. We also examine issues of optimal study design. We advocate initially typing a large panel of ASPs (and no additional family members) with a map of genetic markers evenly spaced at 10-20-cM intervals. We recommend a screening procedure that 1) investigates further all regions with maximum lod scores greater than 1 and 2) excludes from consideration those regions that result in lod scores less than -2 at the smallest genetic effect that is viewed as important to detect. Further investigation of an interval might include typing other available families or family members, typing additional markers in the interval, and carrying out further statistical analyses. This strategy is efficient in the number of genotypings required and focuses attention on regions most likely to harbor a disease gene with a substantial impact on disease risk, while resulting in the pursuit of a manageable number of false-positive linkage results. Modification may be required if insufficient ASPs are available or if families come from a significantly admixed population.

Chromosome Mapping↗

Probable exclusion of GLC1A as a candidate glaucoma gene in a family with middle-age-onset primary open-angle glaucoma.

PURPOSE: To determine whether an adult-onset variety of primary open-angle glaucoma in family UM:POAG1 is linked to the previously mapped GLC1A juvenile-onset primary open-angle glaucoma locus on chromosome 1q or whether linkage can be excluded. METHODS: Microsatellite repeat markers from the 9 cM D1S196 to D1S218 interval containing the GLC1A gene were amplified by polymerase chain reaction from DNA samples collected from 11 members of one sibship in family UM:POAG1. Haplotype analysis was carried out, including calculation of the probability that the observed data would have been obtained if the underlying cause of primary open-angle glaucoma in this family were a defect in a gene located in the tested interval. Linkage analysis was carried out under an autosomal dominant model for GLC1A glaucoma. RESULTS: In family UM:POAG1, primary open-angle glaucoma was diagnosed in six surviving and one deceased member of a sibship of 13 individuals during the fifth or sixth decade of life. Glaucoma in this family has a later average age at diagnosis and significantly less elevation in intraocular pressure than GLC1A glaucoma so far described. Haplotype analysis, using a population prevalence up to 0.9%, shows that it is unlikely that the reported data would have been observed if primary open-angle glaucoma in this pedigree were due to the GLC1A locus on chromosome 1q21-q31. Linkage analysis under the juvenile glaucoma autosomal dominant model allowed exclusion of linkage across the entire GLC1A genetic inclusion interval, with a maximum lod score in the interval of -3.28. CONCLUSION: The most likely interpretation of these observations is that a defect in the GLC1A glaucoma gene is not responsible for adult-onset primary open-angle glaucoma in family UM:POAG1. This suggests the existence of at least two primary open-angle glaucoma genes, the previously reported GLC1A gene on chromosome 1q and another gene located elsewhere in the genome. Diagnosis of UM:POAG1 glaucoma between 42 and 57 years of age also raises questions regarding the relation of the glaucoma present in this family to the common later-age-onset form of the disease.

Adult↗

Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations.

BRCA1 is a breast cancer-related tumor suppressor gene located on human chromosome 17q21. Inherited mutations in BRCA1 are thought to be responsible for approximately half of all inherited breast cancer and to confer increased risk for ovarian, colon, or prostate cancer. Studies of affected families and population-based studies have provided some information on the prevalence of BRCA1 mutations in Caucasian U.S. and European populations as well as on the penetrance of these mutations. We review the available data on the epidemiology of breast cancer with specific reference to BRCA1. In addition, we describe the genetic analysis of one large family with multiple affected individuals now known to harbor a BRCA1 germline mutation but initially identified by genetic linkage analysis. This family is presented as a model of the challenges that can be encountered in genetic analysis of familial forms of cancer. To this end, we compare the outcome of analysis before and after the identification of a mutation that predisposes family members to early-onset breast and ovarian cancers. We describe seven additional families with evidence of linkage between breast cancer and genetic markers in the BRCA1 region. Each of these families generated a 2-point LOD (i.e., logarithm of the odds) score greater than 1.18 for at least one polymorphic marker flanking BRCA1. These families have formed the basis of our efforts to characterize BRCA1 mutations. First-pass mutation analysis using the single-strand conformation polymorphism approach failed to identify any mutations in the seven families. We consider the possible reasons for the apparent low mutation-detection efficiency.

Adult↗

BRCA1 maps proximal to D17S579 on chromosome 17q21 by genetic analysis.

Previous studies have demonstrated linkage between early-onset breast cancer and ovarian cancer and genetic markers on chromosome 17q21. These markers define the location of a gene (BRCA1) which appears to be inherited as an autosomal dominant susceptibility allele. We analyzed five families with multiple affected individuals for evidence of linkage to the BRCA1 region. Two of the five families appear to be linked to BRCA1. One apparently linked family contains critical recombinants, suggesting that the gene is proximal to the marker D17S579 (Mfd188). These findings are consistent with the maximum-likelihood position estimated by the Breast Cancer Linkage Consortium and with recombination events detected in other linked families. Linkage analysis was greatly aided by PCR-based analysis of paraffin-embedded normal breast tissue from deceased family members, demonstrating the feasibility and importance of this approach. One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents the first such family of African-American descent to be reported in detail.

Base Sequence↗

Effects of charcoal-extracted follicular fluid on reproductive function in postpartum cows.

In order to determine the role of follicle-stimulating hormone (FSH) on the resumption of ovarian function in cows early postpartum (PP), bovine follicular fluid (FF) was used to selectively suppress concentrations of FSH. Calves were removed from all cows within 24 hr of birth. Follicular fluid that was treated with charcoal to remove steroids (15 ml; n = 14) or serum (S) from an ovariectomized cow (15 ml, n = 14) was injected i.m. twice daily from days 1 to 10 PP. Blood samples were collected before each injection and frequent samples (every 15 min for 6 hr) taken on days 5 and 10 PP. Eight cows from each group (FF and S) were slaughtered on the morning of day 11 PP and pituitaries and ovaries collected. The remaining cows (n = 6) were observed for estrus. Treatment with FF delayed follicular growth (P less than 0.01), as evidenced by the largest follicle per cow observed at time of slaughter (3.6 +/- 0.42 vs 11.5 +/- 1.77 mm dia; FF vs S). The intervals from parturition to first estrus (P less than 0.11) and to first progesterone rise (25.3 +/- 1.97 vs 18.0 +/- 3.62 d; P less than 0.06) tended to be delayed by treatment with FF vs S. Many of the cows treated with S ovulated by day 10 PP, they were divided retrospectively into those that had ovulated by (n = 9) or after (n = 5) day 10 PP for analysis. Cows treated with FF had lower (P less than 0.05) and less variable (P less than 0.01) serum FSH concentrations while levels of luteinizing hormone (LH) tended (P less than 0.08) to be greater on days 5 and 10 PP. Follicular fluid decreased levels of FSH (P less than 0.001), but not LH (P less than 0.15), in the samples obtained twice daily compared to S-treated cows that did not ovulate by day 10 PP. Anterior pituitaries were dissociated, and cells from each cow were cultured in order to ascertain whether treatment with FF in vivo would affect gonadotropin secretion in vitro. Estradiol-17 beta (E) was incubated with pituitary cells to determine the effect of E on gonadotropin secretion from cells of PP cows, and to ascertain whether treatment with FF in vivo and with E in vitro would interact to affect secretion of FSH and LH in culture. After 2 d of incubation, cells were treated with 10(-9) M E or vehicle (1% ethanol).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Prospective treatment of urea cycle disorders.

We present a diagnostic and therapeutic protocol designed to prevent clinical expression of inborn errors of urea synthesis in the neonatal period, and discuss the long-term developmental outcome of survivors. The families of 32 infants, among 43 identified prenatally as being at risk for a urea cycle disorder, chose to have their infants treated according to a diagnostic and therapeutic protocol, beginning at birth. The therapy was effective in avoiding neonatal hyperammonemic coma and death in seven patients with carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, and argininosuccinate lyase deficiency. When treated prospectively, five of eight patients with ornithine transcarbamylase deficiency avoided severe hyperammonemia and survived the neonatal period. Two patients with carbamoyl phosphate synthetase deficiency and two with ornithine transcarbamylase deficiency have subsequently died; three additional patients with the latter disorder have received orthotopic liver transplants. Our experience suggests that these surviving patients have had a more favorable neurologic outcome than patients rescued from neonatal hyperammonemic coma. However, all of them require a burdensome medical regimen and may have handicaps that include impairment of development and recurrent episodes of hyperammonemia. Further, those with deficiency of carbamoyl phosphate synthetase or ornithine transcarbamylase have a high mortality rate.

Amino Acid Metabolism, Inborn Errors↗

Allopurinol-induced orotidinuria. A test for mutations at the ornithine carbamoyltransferase locus in women.

Ornithine carbamoyltransferase is an X-linked mitochondrial enzyme expressed in hepatocytes and enterocytes. A deficiency of this enzyme results in central nervous system dysfunction, which may be fatal in newborn boys. Milder forms are seen in older boys and girls and in adults. Establishing the carrier status of women at risk for ornithine carbamoyltransferase deficiency is important for determining reproductive and medical risks for affected women. We report a test to establish the carrier status of women at risk for ornithine carbamoyltransferase deficiency. This test relies on the allopurinol-induced accumulation of orotidine, whose synthesis is stimulated by carbamoyl phosphate, a substrate that accumulates in ornithine carbamoyltransferase deficiency. We used anion-exchange, high-performance liquid chromatography to measure urinary orotidine and orotic acid excretion after the administration of a 300-mg oral dose of allopurinol in 25 [corrected] women who were obligate heterozygotes, 13 who were probable heterozygotes, 15 mothers of affected boys from monoplex families (families with only one affected member), 12 mothers of affected girls from monoplex families, and 21 [corrected] normal, unrelated women who were not carriers. Urinary orotidine excretion was increased 3 SD or more above the mean value for the normal women in 95.8 percent of the obligate heterozygotes, 84.6 percent of the probable heterozygotes, 73.3 percent of the mothers of affected boys in monoplex families, and 33.3 percent of the mothers of affected girls in monoplex families, thus establishing that these women were carriers of a mutant ornithine carbamoyltransferase allele. The presence of allopurinol-induced orotic aciduria was not as sensitive or specific an indicator of carrier status as the presence of orotidinuria. We conclude that measurement of urinary orotidine excretion after the administration of allopurinol is a simple and reliable test for the identification of women who are heterozygous for ornithine carbamoyltransferase deficiency.

Adult↗

Variability of ovarian structures and plasma progesterone profiles in dairy cows with ovarian cysts.

Weekly reproductive health examinations were performed on 46 multiparous Holstein cows from 14 to 100 d post partum. Sixteen cows developed 19 nonsimultaneous ovarian cysts, with a mean day of first detection at 34.3 +/- 4.5 d post partum and a mean duration of 31.0 +/- 4.3 d after first detection. Coccygeal blood was collected three times weekly, and plasma progesterone concentrations were determined by radioimmunoassay. Cysts were diagnosed by palpation per rectum or by ultrasonography and classified as follicular or luteal cysts; the cows were not treated. Cows with a mean plasma progesterone concentration of < 1 ng/ml from the first day of detection (Day 1) of a cyst until Day 10 were classified as having a follicular cyst, and those with a mean plasma progesterone concentration of >or= 1 ng/ml from Day 1 to Day 10 were classified as having a luteal cyst. According to this classification, 58% of the cysts were follicular and 42% were luteal. There was an overall 47% agreement between classification by palpation and by ultrasonography on Day 1 with progesterone concentration during Days 1 to 10 after detection of the cyst. Detailed graphs of progesterone concentrations and area of largest follicles or cysts and corpora lutea demonstrate the variability of ovarian structures and progesterone profiles in cystic cows. Detection of a cyst at any one time accompanied by simultaneous measurement of progesterone can lead to different diagnoses of cyst type depending on the method of classification, the presence and age of luteinized tissue in the cyst and undetected corpora lutea.

Journal Article↗

Late-onset ornithine transcarbamylase deficiency in male patients.

We report on 21 male patients who presented after 28 days of age with ornithine transcarbamylase (OTC) deficiency, which we define as late-onset OTC deficiency. These patients appeared normal at birth, but irritability, vomiting, and lethargy, which were often episodic, later developed. The age at presentation ranged from 2 months to 44 years. Biochemical testing revealed hyperammonemia, hyperglutaminemia, hypocitrullinemia, increased urinary orotate excretion, and decreased liver OTC activity measured in vitro, which ranged from 0% to 15% of normal. Male patients who were older at presentation had a somewhat different pattern of presenting symptoms and were more likely to die. These data illustrate the phenotypic variability of OTC deficiency. Unexplained episodes of repetitive or protracted vomiting in association with progressive alterations in behavior or neurologic findings should suggest the diagnosis of a urea cycle defect (or another symptomatic inborn error of metabolism), regardless of the age or medical history of the patient.

Adolescent↗

Effects of fat supplementation and immature alfalfa to concentrate ratio on plasma progesterone, energy balance and reproductive traits of dairy cattle.

Forty-six multiparous Holstein cows were assigned at 5 d postpartum to a completely randomized design employing a 2 x 3 factorial arrangement of treatments. Factors were 0 and 5% added prilled long-chain fatty acids (DM basis) and three forage to concentrate ratios (45:55, 64:36, 84:16). Diets consisted of immature alfalfa silage and a concentrate of shelled corn and soybean meal with or without fat replacing a portion of the corn. Mean plasma concentration of cholesterol was higher for cows fed 5% vs. 0% fat and increased over the first 100 d in milk for all animals regardless of treatment. There were no differences in reproductive performance due to either of the main effects. Mean plasma progesterone was higher due to fat treatment in the mid to late luteal phase of the second postpartum cycle as well as the metestrous to early luteal phase and mid to late luteal phase of the third cycle. Even though progesterone concentrations were higher in cows fed 5% fat during the luteal phase after breeding, the conception rates at this service were not different from those fed 0% fat. The biological significance of increased plasma progesterone concentration was not identified with any postpartum reproductive trait measured in this trial.

Animal Feed↗

The effect of photoperiod on diurnal rhythms of serum gonadotrophins, prolactin and melatonin in ovariectomized heifers.

Fourteen heifers, ovariectomized prepubertally, were used in two experiments to test the hypotheses that (1) there are diurnal patterns in circulating concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin and melatonin and (2) that these diurnal patterns would be altered by changing photoperiod. In experiment 1 (Exp. 1) animals were randomly assigned to either increasing photoperiod (I) (n = 7) or decreasing photoperiod (D) (n = 7) for a period of 8 weeks. In the second experiment (Exp. 2) four heifers from each photoperiod group were assigned to the opposite treatment for another 4 weeks forming four subgroups; continued increasing photoperiod (II) (n = 3), increasing followed by decreasing photoperiod (ID) (n = 4), decreasing followed by increasing photoperiod (DI) (n = 4) and continued decreasing photoperiod (DD) (n = 3). At weeks 4, 8 (Exp. 1) and 12 (Exp. 2) the animals were cannulated and blood samples were taken hourly from 1030 hr to 0830 hr (23 samples). In Exp. 1, animals exposed to either I or D did not differ in circulating concentrations of LH, FSH, prolactin and melatonin. Concentrations of LH and melatonin but not FSH or prolactin were higher in animals during the scotophase than the photophase. In Exp. 2 LH, FSH and prolactin, but not melatonin concentrations were higher in animals exposed to I (II and ID) than D (DI and DD). Animals exposed to I had higher circulating concentrations of FSH and animals exposed to both I and D had higher concentrations of melatonin during the scotophase. Neither LH nor prolactin concentrations differed between scotophase and photophase. The abrupt switch from one photoperiod treatment to the other did not significantly affect LH, FSH or prolactin but did alter the patterns and concentrations of circulating melatonin. Animals that remained in the same photoperiod treatment had similar melatonin concentrations; but animals changed from I to D had higher serum melatonin concentrations than those changed from D to I. These data support the hypothesis that there are diurnal changes in circulating concentrations of melatonin in the prepubertal bovine female, with concentrations higher during scotophase than photophase. In addition, under certain photoperiodic conditions there were diurnal rhythms in gonadotropins. These data also support the hypothesis that changing photoperiod alters the diurnal pattern in circulating melatonin concentrations.

Animals↗

The effect of exogenous melatonin administration on gonadotropin and prolactin patterns in ovariectomized estradiol-treated heifers exposed to increasing photoperiod.

Eight nulliparous Angus and Angus crossbred heifers, which had been ovariectomized and treated with estradiol-17beta (E(2)) S.Q. implants for 6 months, were used to determine the effects of exogenous melatonin on serum gonadotropin and prolactin concentrations. Melatonin (15 mg) or corn oil (vehicle) was administered as a single i.m. injection at 1600 h daily for 12 weeks (March 19 to June 4, 1982). Blood samples taken weekly via jugular venipuncture at approximately 1100 h were assayed for luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin and E(2). At 4-week intervals, animals were fitted with indwelling jugular cannulae at 1100 h and samples were taken for 4 h at 15-min intervals. These samples were used to estimate pulsatile patterns of LH, FSH and prolactin. On the day of the first 15-min sampling, additional blood samples were collected at 30 min intervals from 1500 to 2200 h to determine the acute effect of melatonin injection on concentrations of LH, FSH and prolactin. Melatonin did not affect concentrations of FSH collected at weekly intervals (P=0.03) but tended to inhibit the decrease in concentrations of LH seen in the heifers treated with vehicle (P=0.12). There was a melatonin x time interaction for FSH (P=0.04) and a tendency for this interaction for LH (P=0.11). Circulating concentrations of prolactin were not different between treatment groups (P=0.83) nor was there a melatonin x time interaction (P=0.03). Estradiol was higher in the melatonin treated group (P=0.03) (15.58 +/- 4.17 versus 8.25 +/- 1.25 pg/ml) (X +/- SEM) and the melatonin x time interaction was significant (P=0.001). There was a tendency for a melatonin x time interaction for FSH pulse frequency (P=0.10). Prolactin pulse duration tended to decrease in response to melatonin treatment (P=0.14) (15.92 +/- 9.29 versus 11.04 +/- 4.57 min). These data do not support the hypothesis that melatonin decreases prolactin concentrations in cattle and indicates that other factors must mediate photoperiod regulation of this hormone. However, the interpretation of these data is less clear concerning the hypothesis that melatonin may maintain elevated concentrations of gonadotropins in the presence of increasing photoperiod. Concentrations of FSH appeared to be more affected by melatonin than LH; consistent with previous observations that FSH may be more affected than LH by changes in photoperiod (2). But neither LH or FSH concentrations were clearly shown to be consistantly elevated in the melatonin treatment group.

Journal Article↗

Effect of photoperiod on LH, FSH and prolactin patterns in ovariectomized oestradiol-treated heifers.

Angus and Angus crossbred heifers were ovariectomized, treated with oestradiol implants and randomly assigned to the natural photoperiod of fall to spring for 43 degrees N latitude or extra light simulating the photoperiod of spring to fall. Weekly blood samples were taken for 6 months (fall to spring equinox). All heifers were cannulated every 4 weeks and blood samples were taken for 4 h at 15-min intervals. Sera were assayed for LH, FSH, prolactin and oestradiol. In samples taken weekly, serum LH and FSH concentrations were higher while serum prolactin was lower in heifers exposed to natural photoperiod. There was a photoperiod X time interaction for both FSH and prolactin with concentrations diverging as photoperiod diverged. Circulating concentrations of oestradiol were not different between groups. In samples taken every 4 weeks at 15-min intervals, baseline concentrations of LH and FSH and LH pulse amplitude were higher while prolactin pulse frequency was lower in heifers exposed to natural photoperiod. There was a photoperiod X time interaction for each of these pulsatile characteristics. The correlation between LH and prolactin concentrations estimated from the 15-min samples differed between the two photoperiod treatment groups. The pooled correlation coefficient (r) was -0.12 under natural photoperiod and +0.50 under extra light. There was also a photoperiod X time interaction with negative correlations occurring when photoperiod was decreasing and positive correlations occurring when photoperiod was increasing. These results support the hypothesis that photoperiod alters serum concentrations of LH, FSH and prolactin in cattle.

Animals↗

Effect of photoperiod on LH, FSH, prolactin and melatonin patterns in ovariectomized prepubertal heifers.

Angus and Angus crossbred prepubertal heifers were ovariectomized and randomly assigned to either increasing light simulating the photoperiod of the vernal equinox to the summer solstice (I) or decreasing light simulating the photoperiod of the autumnal equinox to the winter solstice (D) for 43 degrees N latitude. Three blood samples were taken each week for 14 weeks, the first at 11:00 h and two others 2 days later, 1 h before lights on (dark), 1 h before lights off (light). At the end of 14 weeks 4 heifers from each treatment group were cannulated and samples were taken for 12 h at 15-min intervals, 6 h in the light and 6 h in the dark. All sera were assayed for LH, FSH and prolactin. In addition, the samples taken at 15-min intervals were assayed for melatonin. In samples taken weekly at 11:00 h circulating concentrations of LH and prolactin were higher among animals in Group I, while FSH concentrations were not different between Groups D and I. In samples collected weekly in the light or the dark, LH and prolactin concentrations were higher in Group I animals. However, prolactin concentrations were higher and LH concentrations tended to be higher in samples taken in the dark. FSH concentrations were not different between either D or I or dark and light. In samples taken at 15-min intervals the prolactin baseline was higher and pulse amplitude tended to be higher for Group I animals. Neither LH nor FSH pulse characteristics differed between I and D; however, LH baseline and LH pulse amplitude were higher in the dark. Melatonin pulse amplitude was higher among animals in Group D and higher in serum collected in the dark. These results suggest that photoperiod alters circulating concentrations of LH and prolactin and alters pulsatile release of LH, prolactin and melatonin in the prepubertal heifer.

Animals↗

The negative feedback effect of estradiol-17beta on secretion of luteinizing hormone in beef cows.

Thirty-two ovariectomized cows were used to determine the time course for the negative feedback effect of estradiol-17beta (E) on secretion of the luteinizing hormone (LH). The cows were injected with gonadotropin releasing hormone (GnRH; 40 mug) 2.5 or 5 h after pretreatment with E (1 mug/kg body weight) or with a vehicle for control (C). Pretreatment with E resulted in lower serum concentrations of LH at 2.5 h (0.27 vs 0.90 ng/ml; P < 0.01) and at 5 h (0.27 vs 0.67 ng/ml; P < 0.01); less LH was released in response to GnRH at 2.5 h after treatment compared to cows treated with C (10 +/- 4.9 vs 27 +/- 3.8 ng/ml; P < 0.001). However, when GnRH was administered 5 h after E or C, there was no difference in the total amount of LH released (34 +/- 1.8 vs 26 +/- 4.4 ng/ml; P > 0.2). Time to half area (estimate of decay for the induced surge of LH) was longer for cows treated with E when compared to those treated with C (1.3 vs 0.9 h, P < 0.001; 1.5 vs 0.8 h, P < 0.001). Time to half area was not affected by the time of administration of GnRH after E (P > 0.4). These results suggest that E acts in the pituitary to cause the initial decrease in concentrations of LH. Pituitaries in animals pretreated with E regained the capacity to release as much LH at 5 h after treatment as those treated with C at a time when LH concentrations were still suppressed by E. Thus, the hypothalamus or an extra-hypothalamic area may be involved in maintaining the suppression of LH secretion after the initial effect on the pituitary has declined.

Journal Article↗

Effect of suckling on the hypothalamic-pituitary axis in postpartum beef cows, independent of ovarian secretions.

Thirty-two postpartum (PP) cows were used to investigate the effect of suckling on secretion of luteinizing hormone (LH). Calves remained with their dams (suckled; S), or they were removed within 24 h of birth (nonsuckled; NS). To evaluate the relationship between suckling and negative feedback regulation of LH, cows were ovariectomized on Day 5 PP, then injected intravenously with estradiol-17 beta (E) or vehicle (V) on Day 10 PP. To investigate the influence of suckling on the gonadotropin-releasing hormone (GnRH)-induced release of LH, cows were injected with 80 micrograms of GnRH on a single day varying from 18 to 85 days PP. Suckling inhibited the postcastration rise in LH, as LH concentrations increased at a faster rate in NS compared with S cows [0.031 +/- 0.02 ng/(ml X day) LH: P less than 0.05]; this was not influenced by basal amounts of E since amounts did not differ between S and NS cows at ovariectomy (5.37 +/- 0.36 vs. 5.34 +/- 0.48 pg/ml E; P greater than 0.05). Serum concentrations of LH were negatively related to total follicular E only in S cows (r = -0.71; P less than 0.01). Estradiol-17 beta caused a decrease not only in the level but also the variability in LH concentrations in both S and NS cows: LH in S cows was less variable after E than in NS cows (P less than 0.001), but the magnitude of LH suppression was not influenced by suckling (P greater than 0.25). The regression of LH response on days PP was essentially the same over time for both S (P greater than 0.25) and NS (P greater than 0.25) cows, indicating that LH response to a GnRH injection was not influenced by suckling or days PP. Suckled cows had a tendency to release more LH relative to their baseline in response to GnRH as time PP increased (P less than 0.10), but NS cows did not. These results indicate that even though ovarian secretions inhibit LH release from the pituitary, other inhibitory influences may have a major effect in S cows. Concentrations of LH were lower in S cows than NS cows on Day 10 PP, following removal of the ovaries on Day 5, suggesting that suckling had a direct effect on the hypothalamic-pituitary axis.

Animals↗