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Biomedical subjects

M W Vernon

Publications and source records attributed to M W Vernon.

At least 37 records · Page 2Linked to original sources
PubMed1987

The response of cultured gonadotrophs to inhibin: the role of calcium mobilization.

The role of calcium mobilization and calmodulin activation in the induction of the selective suppression of follicle stimulating hormone (FSH) release by the gonadal protein inhibin was assessed employing a rat gonadotroph monolayer culture system. Inhibin, in porcine follicular fluid (60 microliters/ml), did inhibit FSH release in the face of GnRH stimulation. Antagonism of calcium mobilization with verapamil (10(-4) M) and dantrolene (10(-4) M) failed to restore the FSH response when administered with GnRH and inhibin. Trifluoperazine (10(-4) M), a calmodulin antagonist acted similarly. Cellular calmodulin content increased in response to gonadotropin-releasing hormone (GnRH), as did the concentration of cGMP, while both responses were prevented by the administration of inhibin. Trifluoperazine suppressed cGMP concentration to levels below baseline. These data suggest that while calmodulin and the cyclic nucleotides do not mediate the cellular response to inhibin, they may play a role in the control of gonadotropin synthesis. A link may exist between calmodulin, the concentration of which increased in response to GnRH and was suppressed by inhibin, and the elevation of cellular cGMP content induced by GnRH. Further investigation is warranted to assess a possible action of inhibin which is antagonistic to that of calcium in the transduction of GnRH stimulation into FSH release by the pituitary gonadotroph.

Animals↗
PubMed1987

Systematic studies invalidate the neonatally androgenized rat as a model for polycystic ovary disease.

As an adult, the neonatally androgenized (AZ) rat is anovulatory and exhibits follicular cysts. Thus, the AZ rat has been used as a model for polycystic ovary disease (PCO). However, its correlation with the human disease is not clear; so we have studied the AZ rat to determine its suitability as a PCO model. In Experiment I, reproductive hormones were measured at specific intervals between postnatal Days 15 and 90 in saline-treated and AZ rats. In Experiment II, AZ rats were treated with exogenous follicle-stimulating hormone (FSH) or subjected to unilateral ovariectomy (ULO) as analogies to therapies that have been used to treat human PCO. The results demonstrate that the luteinizing hormone (LH), FSH, testosterone (T), and estradiol (E2) concentrations of the AZ rat were not different from control values. Additionally, FSH therapy did not increase the E2 concentrations or the ovarian weight of the AZ rat. Furthermore, control and AZ rats exhibited similar post-ULO rises in FSH, but compensatory ovarian hypertrophy was not evident in the AZ rat. We conclude that 1) the hormonal and morphological patterns observed in the AZ rat do not correlate with those of PCO and 2) the androgenized rat does not provide an adequate model to study PCO.

Adrenal Glands↗
PubMed1987

Androgenic modulation of periovulatory follicle-stimulating hormone release in the rat.

We examined the relationship between the proestrous testosterone (T) surge and periovulatory follicle-stimulating hormone (FSH) release because previous evidence suggested that T may directly stimulate the selective release of FSH on estrus in the rat. In Experiment I, rats received flutamide (F) at either 1200 h on proestrus (F X 1) or 1800 h on Diestrus II and 1200 h on proestrus (F X 2). Additional animals received T-antiserum (T-A/S) at 1800 h on Diestrus II or vehicle (Control) at both times. In Experiment II, ovariectomized (OVX) rats (n = 11) were implanted with estradiol (E2)-filled capsules on Day 5 post-OVX; then, progesterone (P) capsules were implanted for 48 h beginning on Day 7 and again on Day 11. Six of these rats also received T capsules for 6 h on Days 7 and 11. All OVX rats were cannulated on Day 11 and bled every 4 h until they were killed on Day 12. In the first experiment, neither acute androgen receptor blockade with F X 1 nor T-A/S treatment altered the pattern of periovulatory FSH release, suggesting that the proestrous T surge does not directly stimulate estrous FSH release. However, longer blockade with F X 2 suppressed both the proestrous and estrous phases of FSH release, implying that an androgenic stimulus moderates periovulatory FSH release. In Experiment II, E2 and P capsules stimulated gonadotropin surges but not a selective, estrous-like release of FSH. Additional T therapy did not induce estrous-like FSH release again suggesting that surge-like elevations of T do not specifically result in selective FSH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cyclic nucleotides and suppression of follicle-stimulating hormone release by inhibin.

The relative roles of the cyclic nucleotide messengers cAMP and cGMP in the suppression of follicle-stimulating hormone (FSH) secretion in response to inhibin (IBN) were assessed employing rat gonadotropes in monolayer culture. While exposure of cells to gonadotropin-releasing hormone (GnRH) induced a significant increase in the amounts of both FSH and luteinizing hormone (LH) released into the culture medium, these responses were dampened by the administration of IBN (in porcine follicular fluid). Addition of cGMP to the system failed to restore FSH release, while cAMP restored basal FSH release. Modulation of nucleotide metabolism with theophylline, sodium nitroprusside, and a protein kinase inhibitor failed to overcome the IBN-induced suppression of FSH release. The cellular content of calmodulin increased in response to GnRH, a response antagonized by IBN. Cellular levels of cGMP were also increased by GnRH, but this response was unaltered by IBN. The administered drugs all failed to reverse these effects of IBN. These data indicate that the IBN-induced suppression of FSH release is not dependent upon the cyclic nucleotides cAMP and/or cGMP. However, a role in the maintenance of basal FSH synthesis and release for cAMP is indicated.

Animals↗
PubMed1986

Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F.

The severity of the symptoms of endometriosis has not always correlated well with the anatomic severity of the disease. This lack of correlation may be due to variations in the metabolic activity of the endometriotic implants present at different stages of the disease. Because prostaglandin F (PGF) has been implicated as a hormonal mediator of the clinical symptoms of endometriosis, PGF synthesis and content was measured in implants from 14 patients with mild, moderate, severe, or extensive disease. To assess whether PGF production was related to the status of implants, the authors classified implants, based on gross and histologic criteria, as petechial or reddish; intermediate or brown; or powder-burn or black. PGF production of implants from patients with mild or moderate disease was greater than that of implants from patients with severe or extensive disease (P less than 0.05), and PGF content was similar for all stages of endometriosis. Petechial implants produced twice the amount of PGF than intermediate implants (P less than 0.05), which in turn produced more PGF than powder-burn implants (P less than 0.05). Powder-burn implants did not have the in vitro capacity to produce PGF, and the amount of PGF contained in implants of all classes was similar. Therefore, endometriotic implant PGF production and possibly other biochemical activities are dependent on the physical status of the implant. The classification of implants by morphologic appearance may afford additional assistance in determining the prognosis of the disease and in the examination of the subtle effects of the disease on symptoms.

Adult↗
PubMed1985

Studies on the surgical induction of endometriosis in the rat.

As a model to examine the pathophysiologic attributes of endometriosis, attempts were made to surgically induce the disease in the rat by autotransplanting endometrial or uterine tissue to the peritoneum. Rats (n = 46) were randomly assigned to one of four surgical techniques: (1) four uterine squares sutured to the peritoneal cavity; (2) uterine luminal lavages instilled into the peritoneal cavity; (3) endometrial scrapings flushed into the peritoneal cavity; and (4) sham-operated controls. Rats were examined at various days after surgery for the presence of endometrial implants. The autotransplantation of uterine squares to the peritoneal cavity was the only treatment that yielded healthy endometriotic implants. These implants grew into ellipsoidal cystic structures that were composed of both endometrial glands and stroma and were found to contain prostaglandin F (202 ng/mg) at concentrations similar to those measured in uterine tissue (205 ng/mg). To examine the effect of surgically induced endometriosis upon fecundity, rats (n = 40) were autotransplanted with uterine squares or were sham operated and mated. The presence of ectopic endometrial tissue reduced the number of pups at term by 48% and the number of day 14 embryos by 28% (P less than 0.05). Peritoneal adhesions were greater in rats with induced endometriosis than in sham-operated controls (P less than 0.05); however, in rats with induced endometriosis, no differences were noted in the severity of adhesions between pregnant and nonpregnant rats. Endometriotic implants underwent complete regression in the day 14 pregnant rat but had doubled in size in the nonpregnant rat. At term, the endometriotic implants were larger than in the day 14 pregnant rat (P less than 0.05) and similar to their original size. The successful growth and development of surgically transplanted endometrial tissue in the rat offers a research model that can be used to study those aspects of endometriosis that cannot be adequately investigated in women.

Analysis of Variance↗
PubMed1984

Effect of exogenous gonadal steroids and pregnancy on uterine luminal prostaglandin F in mares.

Two experiments were conducted to assess the effect of exogenous hormone treatment on uterine luminal prostaglandin F (PGF). In the first experiment ovariectomized pony mares received either corn oil (21 days, n = 3), estradiol valerate (21 days, n = 3), progesterone (21 days, n = 3) or estradiol valerate (7 days) followed by progesterone (14 days, n = 4). Progesterone treated mares had higher (P less than .01) uterine luminal PGF compared with all other groups, and no differences were detected between other treatment comparisons. In Experiment II, uterine fluid was collected from 4 ovariectomized horse mares before and after treatment with estradiol valerate (7 days) followed by progesterone (50 days). Pretreatment uterine luminal PGF levels were lower (P less than .001) than post-treatment levels (.03 vs 76.80 ng/ml). In a third experiment PGF was measured in uterine fluid of pony mares on days 8, 12, 14, 16, 18 and 20 of the estrous cycle and pregnancy. In nonpregnant mares a day effect (P less than .03) was observed in which uterine fluid PGF increased during the late luteal phase and declined thereafter. In contrast, no day effect was observed in pregnant animals and uterine luminal PGF was lower (P less than .001) than in cycling animals. These studies indicate that exogenous progesterone administration results in a large increase in uterine luminal PGF, whereas, pregnancy results in suppression. Taken collectively with previous work from our laboratory, these results suggest that while the endometrium of pregnant mares is capable of producing large amounts of PGF, the presence of a conceptus impedes its synthesis and/or release which allows for luteal maintenance.

Animals↗
PubMed1984

Endocrine aspects of early pregnancy in pony mares: a comparison of uterine luminal and peripheral plasma levels of steroids during the estrous cycle and early pregnancy.

Comparisons of estrone, 17 beta-estradiol, and plasma progestin concentrations were made in uterine fluid and peripheral blood of nonpregnant and pregnant pony mares. Concentrations of these steroids were also measured within yolk sac fluid from blastocysts on days 12, 14, 16, and 18 of pregnancy to obtain more complete analyses of the uterine environment (uterine fluid plus yolk sac fluid) of early pregnancy. Thirty mares were randomly assigned to six treatment groups (n = 5/group), and uterine fluid and peripheral blood samples were obtained on days 8, 12, 14, 16, 18, and 20 postovulation. After a recovery period of one estrous cycle, mares were bred at their next estrus. Animals were hysterectomized on the same treatment day to which they had previously been assigned in the nonpregnant phase of this study. Using this design, uterine fluid and peripheral blood samples were collected from each mare on equivalent days of the estrous cycle and pregnancy. Significant differences in day trends were found between nonpregnant and pregnant animals for estrogens and progestins in both uterine fluid and peripheral plasma. Furthermore, these data demonstrate that large increases in estrogens occur after day 12 of pregnancy in uterine and yolk sac fluids, with estrone becoming the predominant estrogen by days 18 and 20 in yolk sac and uterine fluids, respectively. These changes were not detected in peripheral plasma, which indicates that changes occurring within the uterine environment are not discernible in the systemic circulation during early pregnancy. These results indicate that the large amounts of estrogens appearing in uterine fluids during early pregnancy are of conceptus origin and may be an important factor in regulating the environment in which the conceptus develops.

Animals↗
PubMed1984

A rapid method for repurifying partly degraded radiolabeled steroids.

This rapid method for repurifying radiolabeled steroids from degraded products is based upon differential partitioning of intact and degraded molecules between aqueous-phase solution and anhydrous diethyl ether. Results compare favorably with those by liquid-chromatographic methods.

Chromatography, High Pressure Liquid↗
PubMed1982

Effect of pregnancy and collection technique on prostaglandin F in the uterine lumen of Pony mares.

Uterine flushings were obtained through the cervix (Method A) and through the wall of the uterus after hysterectomy (Method B) of ovariectomized Pony mares after s.c. injection of oestrogen for 1 week and progesterone for 2 weeks (Exp. 1). Non-pregnant and pregnant mares were flushed by Method A on Day 14 after ovulation and the flushings compared with those of non-pregnant mares injected i.v. with flunixen meglumine, a prostaglandin synthetase inhibitor, shortly before flushing (Exp. 3). Uterine flushings were also collected by Methods A and B from non-pregnant and pregnant Pony mares on Day 14. Endometrial and embryonic tissues from these mares were incubated with and without flunixen meglumine (Exp. 3). In all experiments, pregnancy had a significant effect on PGF content of uterine flushings or incubation media. Flushings from pregnant mares had reduced levels of PGF and were not influenced by collection technique (Exps 1 & 3). Non-pregnant Pony mares treated with progesterone responded to cervical stimulation (Method A) with an increase in intrauterine PGF over levels measured after hysterectomy (Method B) (Exps 1, 2 & 3). There was no effect on endometrial production of PGF in vitro by any tissue combination in a 2 h incubation in Krebs-Ringer-bicarbonate buffer but after 12 h incubation in Minimum Essential Medium endometrial PGF production was significantly higher when the endometria were from pregnant mares than from non-pregnant mares. PGF production in vitro was significantly suppressed by flunixen meglumine, by yolk sac membranes, and yolk sac and trophoblast, but not by trophoblast alone. The low intrauterine PGF levels in pregnant mares and the low in-vitro PGF production in the presence of the conceptus membranes may reflect inhibition of PGF synthesis and/or release by the embryo.

Animals↗
PubMed1979

An investigation of the uterine luminal environment of non-pregnant and pregnant pony mares.

Uterine flushings were collected from 30 non-pregnant Pony mares on Days 8, 12, 14, 16, 18 or 20 after oculation. Mares were allowed a recovery period of one oestrous cycle and were mated at the next oestrus. They were then ovario-hysterectomized on days which corresponded to the day of the oestrous cycle to which they were assigned. Uterine flushings were analysed for total recoverable protein and acid phosphatase activity. Least squares analysis indicated a status X day interaction for total protein (P less than 0.10) and acid phosphatase activity (P less than 0.005) in which the latter was higher in uterine flushings during pregnancy. Peripheral plasma oestrone and oestradiol concentrations were measured by radioimmunoassay and results indicated that plasma oestrone concentrations in pregnant and non-pregnant mares were not different, and oestradiol was lower (P less then 0.005) in the peripheral plasma during pregnancy. conceptus membranes were incubated in vitro for 120 min in a chemically defined medium. Incubation medium was then assayed to assess oestrone and oestradiol production capacilities at Days 8, 12, 14, 16, 18 and 20 of pregnancy. Conceptus membrane production of oestradios (pg/5 ml/h) increased (P less than 0.05) from Day 8 (243 pg/5 ml) to Day 20 (108 763 pg/5 ml). A similar trend, but of lower magnitude, existed for oestrone production.

Acid Phosphatase↗
PubMed1979

Specific PGF-2 alpha binding by the corpus luteum of the pregnant and non-pregnant mare.

The binding of prostaglandin (PG) F-2 alpha to corpora lutea (CL) from pregnant and non-pregnant Pony mares was examined. Studies of the rates of association and dissociation indicated that [3H]PGF was bound specifically and reversibly to a luteal cell membrane preparation (MP) that was isolated by high speed (100,000 g) ultracentrifugation. Various PGs and PG metabolites displaced [3H]PGF from the receptors in the following decreasing order: PGF-2 alpha greater than 13, 14-dihydro-PGF-2 alpha = 13,14-dihydro-15-keto PGF-2 alpha greater than PGD-2 greater than PGF-1 alpha = PGE-2 greater than PGE-2 beta greater than PGE-1. These data implicate the 9 alpha-OH and 5,6 cis double bond as major contributors to PGF receptor recognition. The membrane preparation appeared to contain at least two receptor populations, a high affinity, low capacity and a low affinity, high capacity receptor. The binding of PGF (pg/mg MP protein +/- s.e.m. (n)) to CL of the non-pregnant mare increased from 4.09 +/- 11.6 (4), on Day 4 after ovulation, to reach maximal levels by Day 12, 15.01 +/- 2.5 (4), and declined thereafter. In pregnancy the binding of PGF continued to increase until Day 18, reaching 27.47 +/- 1.7 (3), before it declined on Day 20. The reduction in binding by Day 16 in the non-pregnant mare may reflect the process of luteolysis, while high PGF binding capacity of CL between Days 16 and 18 of pregnancy indicated that luteal maintenance during pregnancy is not associated with a reduction of PGF binding capabilities.

Animals↗
PubMed1979

Alteration of seasonal reproductive patterns in mares following superior cervical ganglionectomy.

Oestrous behaviour, ovarian follicular development, ovulation and changes in hair coat were observed in Pony mares which were unoperated, sham-ganglionectomized control or bilaterally superior cervical ganglionectomized. Surgery was performed during the winter anoestrus (1975--1976). Reproductive patterns in all groups were similar during the first breeding season (1976) after operation but in ganglionectomized mares the onset of the next breeding season (date of first ovulation in 1977), the pattern of follicular development, date of first oestrus and pattern of hair coat changes were all significantly delayed relative to those of the non-operated and sham-operated mares in 1976 and 1977 and relative to their own patterns in 1976. These results indicate that the pineal-hypothalamo-pituitary axis may regulate or moderate annual reproductive rhythms in mares.

Animals↗