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Biomedical subjects

M E Wise

Publications and source records attributed to M E Wise.

At least 19 recordsLinked to original sources
PubMed1992

Progesterone directly inhibits pituitary luteinizing hormone secretion in an estradiol-dependent manner.

We recently demonstrated that progesterone and estradiol inhibit pituitary LH secretion in a synergistic fashion. This study examines the direct feedback of progesterone on the estradiol-primed pituitary. Nine ovariectomized (OVX) ewes underwent hypothalamic-pituitary disconnection (HPD) and were infused with 400 ng GnRH every 2 h throughout the experiment. After 7 days of infusion, estradiol was implanted s.c. Four days later, estradiol implants were exchanged for blank implants in 4 ewes and for progesterone implants in 5 ewes. These implants remained in place for another 4 days. Blood samples were collected around exogenous GnRH pulses before and 0.5 to 96 h after implant insertion and exchange. Serum LH and progesterone concentrations were determined through RIA. One month later, 4 of the HPD-OVX ewes previously implanted with steroids were reinfused with GnRH and the implantation protocol was repeated using blank implants only. In estradiol-primed ewes, progesterone significantly lowered LH secretion after 12 h of implantation and LH secretion remained inhibited while progesterone implants were in place (p less than 0.05). Removing estradiol transiently lowered LH secretion, and this effect was significant only 24 h after estradiol withdrawal (p less than 0.05). These data suggest that progesterone has a direct, estradiol-dependent inhibitory effect on pituitary LH release and that estradiol may sustain pituitary gonadotrope response to GnRH.

Animals↗
PubMed1991

Pineal melatonin inhibition of tumor promotion in the N-nitroso-N-methylurea model of mammary carcinogenesis: potential involvement of antiestrogenic mechanisms in vivo.

The N-methyl-N-nitrosourea (NMU) model of hormone-responsive rat mammary carcinogenesis was used to address the hypothesis that melatonin (Mel), the principle hormone of the pineal gland, inhibits tumorigenesis by acting as an anti-promoting rather than an anti-initiating agent. Daily late-afternoon injections of Mel (500 micrograms/day), restricted to the initiation phase of NMU mammary tumorigenesis, were ineffective in altering tumor growth over a 20-week period. When Mel treatment was delayed for 4 weeks after NMU and then continued through the remainder of the promotion phase, only tumor number was significantly lower than in controls. However, when Mel injections encompassed the entire promotion phase, both tumor incidence and number were significantly lower than in the controls. Although elimination of the endogenous Mel signal via pinealectomy promoted tumor growth, the effect was not statistically significant. Serum levels of estradiol and tumor estrogen receptor content were unaltered by either Mel or pinealectomy. While Mel treatment failed to affect circulating prolactin levels, pinealectomy caused a two-fold increase in serum prolactin. The estradiol-stimulated recrudescence of tumors following ovariectomy was completely blocked by either 20, 100 or 500 micrograms Mel/day or tamoxifen (20 micrograms/day). Thus, Mel appears to be an anti-promoting hormone that may antagonize the tumor-promoting actions of estradiol in this model of mammary tumorigenesis.

Animals↗
PubMed1991

Advancement of postnatal pulsatile luteinizing hormone secretion in the bull calf by pulsatile administration of gonadotropin-releasing hormone during infantile development.

The transition from infantile to prepubertal development in bull calves coincides with the onset of postnatal LH secretion following differentiation of pituitary gonadotropes. Increased pulsatile secretion of hypothalamic GnRH may contribute to maturational development of the hypothalamic-pituitary axis. To evaluate the role of GnRH pulse frequency in mediating changes in pituitary response that may lead to altered LH release, serum LH concentrations in Holstein bull calves treated with exogenous GnRH were examined. Nine calves received 200 ng GnRH for 5 min every hour from 1-6 wk of age (GnRH-T), while 5 animals served as controls. Weekly through 6 wk of age, jugular venous blood was collected every 10 min for 8 h. Blood samples from GnRH-T animals were taken during 2 exogenous GnRH pulses followed by 6 h of sampling without exogenous GnRH. Mean serum LH concentrations were greater (p less than or equal to 0.01) in GnRH-T calves than in controls at 2 through 6 wk of age. LH pulse height did not change in either group during the study period. However, LH pulse frequency in GnRH-T calves increased with age (P less than or equal to 0.01), and at 4-6 wk of age, the rate of pulsatile LH secretion was greater (p less than or equal to 0.01) in GnRH-T calves than in controls. Pituitary LH content increased 2.4-fold after GnRH infusion (p less than or equal to 0.01); this increase was associated with a doubling of the pituitary LH-beta mRNA concentration found in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Direct pituitary effects of estradiol and progesterone on luteinizing hormone release, stores, and subunit messenger ribonucleic acids.

To determine the direct, chronic actions of progesterone (P4) and estrogen (estradiol, E2) on anterior pituitary synthesis and release of LH, 24 western range ewes underwent hypothalamic-pituitary disconnection (HPD) and ovariectomy (OVX) during the breeding season and were pulsed with exogenous GnRH with or without steroid replacement. Sequential blood samples were collected before infusion of GnRH and on Days 7 and 14 of GnRH infusion. Silastic capsules of P4 and/or E2 were implanted s.c. on Day 7 and remained in place throughout the experiment. Control ewes received only GnRH infusion. Blood sampling was centered around three exogenous GnRH pulses. After the final blood sampling, pituitaries were collected and stored at -70 degrees C. Concentrations of LH in serum and pituitaries were determined by RIA. Relative concentrations of LH subunit mRNAs were determined by Fast Blot analysis. Simultaneous implantation of P4 and E2 lowered LH pulse amplitude 70% and mean serum levels 30% compared with controls. Neither steroid alone affected LH release. E2 alone or in combination with P4 lowered LH-beta subunit mRNA concentrations 40% compared with controls while alpha-subunit levels were unchanged. Only E2 alone altered the pituitary content of LH, causing a 60% decrease. We conclude that the combination of P4 and E2 is necessary for inhibition of GnRH-stimulated LH secretion. E2 inhibits GnRH-stimulated LH-beta subunit mRNA concentrations but does not affect alpha-subunit mRNA concentrations. The control of pituitary LH content by P4 and E2 is the result of changes in both LH-beta subunit mRNA concentrations and LH secretion.

Animals↗
PubMed1990

Gonadotropin-releasing hormone secretion during the postpartum anestrous period of the ewe.

An increase in episodic release of LH is putatively the initial event leading to the onset of postpartum ovarian cyclicity in ewes. This experiment was conducted to determine the relationship between hypothalamic release of GnRH and onset of pulsatile secretion of LH during postpartum anestrus. Control ewes (n = 7) were monitored during the postpartum period to determine when normal estrous cycles resumed. In controls, the mean interval from parturition to the first postpartum estrus as indicated by a rise in serum progesterone greater than 1 ng/mg was 25.8 +/- 0.6 days. Additional ewes (n = 4-5) at 3, 7, 14, and 21 days postpartum (+/- 1 day) were surgically fitted with cannula for collection of hypophyseal-portal blood. Hypophyseal-portal and jugular blood samples were collected over a 6- to 7-h period at 10-min intervals. The number of GnRH pulses/6 h increased (p less than 0.05) from Day 3 postpartum (2.2 +/- 0.5) to Days 7 and 14 (3.6 +/- 0.2 and 3.9 +/- 0.4, respectively). A further increase (p less than 0.05) in GnRH pulse frequency was observed at Day 21 postpartum (6.4 +/- 0.4 pulses/6 h). Changes in pulsatile LH release paralleled changes observed in pulsatile GnRH release over Days 3, 7, 14, and 21 postpartum (0.83 +/- 0.3, 2.8 +/- 0.4, 2.9 +/- 0.6, and 4.0 +/- 1.1 pulses/6 h, respectively). GnRH pulse amplitude was higher at Day 21 than at Days 3, 7, or 14 postpartum. These findings suggest that an increase in the frequency of GnRH release promotes the onset of pulsatile LH release during postpartum anestrus in ewes.

Anestrus↗
PubMed1990

Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: I. Alterations in cytosolic-free calcium levels and calcium flux.

The effect of prostaglandin F2 alpha (PGF2 alpha) on cytosolic calcium homeostasis was studied in suspensions of ovine large or small luteal cells from superovulated ewes. In large cells loaded with fura-2 (AM), resting cytosolic-free calcium ([Ca2+]i) was 62 +/- 5 nM (Hanks' medium, pH 7.15), and PGF2 alpha (0.5 microM) induced a rapid transient increase in [Ca2+]i to 152 +/- 6 nM, which then decreased to 97 +/- 6 nM within 3 min and remained at this level for the remainder of the treatment period (10-20 min). PGF2 alpha did not alter intracellular pH (pHi) in cells loaded with snarf-1 (AM) (pHi indicator). The transient nature of the [Ca2+]i increase was due, at least in part, to the ability of PGF2 alpha to stimulate (P less than 0.05) 45Ca2+ efflux. In small cells, resting [Ca2+]i was 57 +/- 5 nM, and no change in [Ca2+]i levels or pHi occurred with the addition of PGF2 alpha. PGF2 alpha also did not affect 45Ca2+ efflux in small cells. Calcium uptake was not significantly altered by PGF2 alpha in large or small cells. Data from kinetic analysis of the calcium transient was best fit to a two-compartment model consisting of a rapidly effluxing compartment and a slowly effluxing compartment. The size and rate constants were 62 +/- 10 nM and 3.6 +/- 1 min-1, respectively, for the rapidly effluxing compartment and 140 +/- 9 nM and 0.02 +/- 0.002 min-1, respectively, for the slowly effluxing compartment. These results provide evidence for a direct effect of PGF2 alpha specifically on the ovine large luteal cell that involves alterations in [Ca2+]i and calcium flux. This effect is likely to be involved in intracellular mediation of the signal for luteal regression.

Animals↗
PubMed1989

Two exceptional sets of physiological clearance curves and their mathematical form: test cases?

Amiodarone concentrations y(t) have been measured from 1 min to more than 50 days following 10 min of infusion, with about 40 observations on each of six normal subjects (Tucker et al., 1984, Eur. J. clin. Pharmacol. 26, 655-656). The form of the log-log plots-ln(y) vs ln(t)--is investigated. These appear to show three phases. First there is a rapid decrease of y(t), then a straight line corresponding to a small negative power of t, ca -0.3, and this line changes continuously but quickly at about 0.5 day into a steeper line that is almost straight. For the curve fitting a simple "spline-type" device was successful. Two continuity conditions were imposed at the time of changeover, which was one of the unknown parameters. The results are compared in detail with those from a set of 15 radiocalcium curves obtained during 2 weeks or more from a single injection of 47Ca (Neer et al., 1967, J. clin. Invest. 46, 1364-1379). Again two power functions of time can be seen. The changeover is much more gradual than with amiodarone, and the fits are still better. Both sets of curves are fitted with fewer adjustable parameters than with the usual multiexponentials that are interpreted in terms of homogeneous compartments. Theoretical and practical implications are mentioned. There is much indirect evidence that hundreds of other clearance curves may consist largely of one or two of such power functions of time.

Amiodarone↗
PubMed1989

Ontogeny of pulsatile secretion of gonadotropin-releasing hormone in the bull calf during infantile and pubertal development.

During the infantile period of development in the bull calf (birth to 6 weeks of age), there is a virtual absence of episodic secretion of LH. Transition from infancy to the prepubertal period (6-10 weeks of age) is characterized by the onset of episodic LH release. This study was conducted to characterize the ontogeny of episodic GnRH release during these developmental periods. During the primary experiment, calves at 2, 5, 8, and 12 weeks of age (n = 4/age) were surgically fitted with cannulae for the collection of mixed hypophyseal portal and cavernous sinus blood. Hypophyseal portal and cavernous sinus and jugular blood samples were collected over a 9- to 12-h period at 10 min intervals. No pulses of LH were observed in calves at 2 or 5 weeks of age. At 8 and 12 weeks of age, pulsatile LH release became evident with a mean of 1.0 +/- 0.3 and 2.20 +/- 0.7 pulses/10 h, respectively. Unlike LH secretion, calves at both 2 and 5 weeks of age released GnRH in a pulsatile manner (3.5 +/- 0.2 and 5.0 +/- 0.6 pulses/10 h, respectively). The frequency of pulsatile GnRH release increased from 7.9 +/- 0.4 pulses/10 h at 8 weeks of age to 8.9 +/- 0.7 pulses/10 h at 12 weeks of age. These findings demonstrate the presence of pulsatile secretion of GnRH during the infantile period of development. Furthermore, the postnatal ontogeny of pulsatile LH release in this species is associated with an increase in the frequency of pulsatile GnRH secretion.

Aging↗
PubMed1988

In-vitro and in-vivo responsiveness of the corpus luteum of the mare to gonadotrophin stimulation.

Dispersed horse luteal cells were used to evaluate the ability of horse LH, hCG and PMSG to stimulate progesterone secretion in vitro. Morphological characterization of these cells before gonadotrophin stimulation indicated the presence of two populations of cells based on cell diameters. In luteal cells incubated as suspended cells, horse LH and hCG stimulated (P less than or equal to 0.05) progesterone production at all levels of treatment. Stimulation of progesterone secretion by hCG was greater (P less than or equal to 0.05) than by horse LH over the range of concentrations utilized. When mares (N = 7) received an intramuscular injection of 1000 i.u. hCG on Days 3, 4 and 5 after the end of oestrus, there was an increase (P less than or equal to 0.05), in peripheral progesterone concentrations beginning on Day 7 and continuing until Day 14 compared with controls (N = 7). Peripheral progesterone concentrations continued to be elevated in hCG-treated mares for Days 15-30 after oestrus in those mares that conceived. Although treatment with hCG increased progesterone concentrations, it had no influence on anterior pituitary release of LH as measured by frequency and amplitude of LH discharge. We conclude that the mare corpus luteum is responsive to gonadotrophins in vitro and that exogenous hCG can enhance serum progesterone concentrations throughout the oestrous cycle and early pregnancy.

Animals↗
PubMed1988

Hormonal alterations in the lactating dairy cow in response to thermal stress.

The influence of acute exposure to thermal stress on the secretion of progesterone, estradiol, cortisol, and LH was monitored in 14 lactating Holstein cows. Eight cows were maintained throughout the summer in a refrigerated air-conditioned tie stall barn. An additional eight cows were maintained in outdoor corrals with access only to shade. Rectal temperatures and respiration rates of cows under heat stress conditions were elevated above the cows maintained under air conditioning. Cows in both environments exhibited similar serum concentrations of progesterone and estradiol throughout the estrous cycle. Serum cortisol concentrations were higher in heat-stressed cows compared to cows maintained under cooling. The number of LH pulses on d 5 of the estrous cycle was greatly reduced in the heat-stressed cows compared to the cows under cooling. No differences in the number of pulses of LH were observed on d 12 of the estrous cycle between cows in the two environments. Data suggest that heat stress can suppress anterior pituitary release of LH without having a measurable influence on ovarian steroid hormone secretion.

Animals↗
PubMed1987

Gonadal regulation of LH secretion in prepubertal bull calves.

In the present study we examined the influence of castration and exogenous estradiol on pulsatile LH release during the transition from infancy to the prepubertal period of development. Bull calves were assigned to treatments (N = 5 treatment) at 6 weeks of age. Treatments consisted of intact controls, castrates and castrates receiving estradiol implants. Plasma LH response was monitored over 8 hr periods at 7, 8, 9, 10, 11 and 13 weeks of age. Castration alone did not alter LH concentrations, compared to controls until 10 weeks of age. At 10, 11 and 13 weeks, mean LH concentration and the number of LH pulses/8 hr period were greater (P less than .05) in castrates than in controls. In castrates with estradiol implants, mean LH concentration and the number of LH pulses/8 hr period were suppressed at all ages compared to controls and castrate treatments. These results indicate that LH release is not inhibited by gonadal factors from 6 to 9 weeks of age in the bull calf. However, estradiol negative feedback on LH secretion is evident during this same developmental period.

Aging↗
PubMed1986

Changing relationships between stature and lung volumes during puberty.

In a follow-up study the relationship between growth in body dimensions and in lung volumes during the adolescent growth spurt was studied in 149 girls and 477 boys, aged 11.5-14.0 years at the start of the study. Total lung capacity (TLC), residual volume, vital capacity (VC) and series dead space were measured twice a year for 6 years. When analyzed cross-sectionally lung volumes can be described by a power function of stature, both for each set of half-yearly measurements and when all data are pooled. The powers were close to 3, increasing at each time of measurement in boys and decreasing in girls. These trends reflect that in each subject the growth spurt does not start at the same age, and that individual growth occurs non-linearly along a steeper line than found in the cross-section. Using simple allometric relationships between stature and lung volumes, volume predictions are too high in the youngest age group, and too low in the oldest adolescents. Including age in the regression equation removes this trend in the cross-sectional data, and for VC and TLC also in the longitudinal data.

Adolescent↗
PubMed1986

Random walk type models for indicator-dilution studies: comparison of a local density random walk and a first passage times distribution.

The relative merits of the local density random walk and the first passage times distributions were compared with respect to their practical applicability in cardiovascular research and clinical practice. Open indicator-dilution curves of varying shape were used, and reference values for area and mean transit times were calculated numerically. Curves not perturbed by recirculation were obtained in two different ways. Thermodilution curves were obtained in an animal model at the left and the right side of the heart respectively and conductivity curves with 0.5% NaCl solution as indicator were obtained in a hydrodynamic circulation model. The fits of the two types of distribution were equally accurate for the more symmetrical curves; for very skewed curves the local density random walk fit proved to be more accurate. This result could be related to the greater difference in shape between the first passage times and local density random walk distribution for a large degree of asymmetry. For this reason the local density random walk distribution for fitting indicator-dilution curves was used in a variety of other experimental conditions.

Animals↗
PubMed1986

Prepubertal changes in the hypothalamic-pituitary axis of Holstein bulls.

We investigated the nature and sites of changes in the hypothalamic-pituitary axis associated with the onset of high-frequency, high-amplitude discharges of luteinizing hormone (LH) in young bulls during the transition from the infantile to the prepubertal phase of development. Blood serum and neuroendocrine tissues from bulls killed at 1, 6, 10, 14, or 18 wk of age were evaluated. Concentrations of LH in serum from bulls 1 or 6 wk old averaged less than 0.25 ng/ml and only one episodic discharge of LH was detected for 10 bulls. At 10, 14, or 18 wk, 14 of 15 bulls had episodic discharges of LH. Concentrations of testosterone in serum were progressively higher at 10, 14, and 18 wk, but the concentration of estradiol was maximal at 6 wk. The concentrations of gonadotropin-releasing hormone (GnRH) in the anterior hypothalamus, posterior hypothalamus, or median eminence were not influenced by age. However, concentration of GnRH receptors in the anterior pituitary gland increased 314% between 6 and 10 wk and the concentration of LH increased 67%. Between 6 and 10 wk, concentrations of estradiol receptors in the anterior and posterior hypothalamus declined by 68% and 46%, but the concentration of estradiol receptors in the anterior pituitary gland increased by 103%. For most characteristics, there was no major change between 10 and 18 wk. We postulate that between 6 and 10 wk of age, there is 1) removal of an estradiol-mediated block of GnRH secretion and 2) an estradiol-mediated, and possibly GnRH-mediated, increase in pituitary GnRH receptors. Together, these changes result in greatly increased stimulation of the anterior pituitary gland by GnRH between 6 and 10 wk of age and stimulation of the discharges of LH characteristic of bulls in the early prepubertal phase of development.

Animals↗
PubMed1986

Functional changes in luteinizing hormone-secreting cells from pre- and postpartum ewes.

Luteinizing hormone (LH)-containing cells from ovine pituitaries obtained during gestation and at various times after parturition were examined to determine whether the ability to store and secrete LH in vitro was correlated with morphological changes. Pituitaries collected on days 50 and 140 of gestation and on days 2, 13, 22, and 35 after parturition were enzymatically dissociated and the resulting cells cultured in media containing estradiol (12 pg/ml), cortisol (12 ng/ml), or no steroid. After 4, 7, or 10 days of culture, cells were washed and basal LH, gonadotropin-releasing hormone (GnRH)-stimulated release of LH, and cellular content of LH were determined. The content of LH (ng/10(6) cells) was lowest on day 140 of gestation (2.7 +/- 0.3) and day 2 postpartum (2.2 +/- 0.6) and then increased (P less than 0.05) on days 13 (36.6 +/- 8.3), 22 (59.9 +/- 14.4), and 35 (54.6 +/- 19.3) postpartum. The percentage of pituitary cells containing immunoreactive LH nearly doubled (P less than 0.05) between days 2 (5.6 +/- 0.2%) and 35 (10.6 +/- 1.1%) postpartum. Moreover, LH-containing cells were smaller, and the percent total cellular volume occupied by secretory granules was less on day 2 than on days 22 and 35 after parturition. Secretion of LH after 4, 7, or 10 days of culture reflected the cellular content of LH and was not influenced by the presence of steroids in the media. These data indicate that decreased synthesis of LH during gestation is associated with hypoplasia of the LH-secreting cells. These cells are reactivated during the postpartum period and their capacity to synthesize LH gradually returns to normal.

Animals↗
PubMed1986

Changes in the concentration of hypothalamic and hypophyseal receptors for estradiol in pregnant and postpartum ewes.

The sensitivity of the hypothalamic-pituitary axis to estradiol was evaluated by monitoring changes in the concentration of receptors for estradiol during gestation and the postpartum period of the ewe. Ewes that had been bred during anestrus so that lambing would occur during the breeding season were killed on d 50 and 140 of gestation or on d 2, 13, 22 and 35 postpartum. Total cytosolic receptors for estradiol were quantified in the anterior and posterior hypothalamus, median eminence, anterior pituitary and cerebral cortex. Concentration and total number of receptors for estradiol in the anterior and posterior hypothalamus and anterior pituitary gland during gestation through d 13 postpartum were similar but increased (P less than .05) by d 22 and 35 postpartum. Changes in the concentration of receptors for estradiol were tissue-specific because stage of reproduction did not influence the number of receptors for estradiol in the median eminence or cerebral cortex. Increases in the concentration of receptors for estradiol in hypothalamic and pituitary tissues on d 22 postpartum immediately preceded the onset of normal ovarian cyclicity in ewes. From these data we conclude that resumption of reproductive cycles in postpartum ewes occurs about the time concentrations of receptors for estradiol in the anterior pituitary gland and hypothalamus increase.

Animals↗
PubMed1985

Negative power functions of time in pharmacokinetics and their implications.

When a clearance curve in pharmacokinetic studies--and in tracer kinetics in general--is well fitted by a sum of negative exponentials of time, in very many cases the data would also be well fitted over much or all of the same period by a function of time consisting mainly of a negative power or by a gamma function. There are also instances where two such power functions can be observed in the same clearance curve. Examples are given from numerous reanalyses of published results. These facts have not been explained, except as being fortuitous, by any existing theory or model based on two or more homogeneous compartments. Theoretical and practical implications are outlined and some general recipes are put forward with a view to replacing multicompartmental analysis.

Administration, Oral↗