Androgen and estradiol effects on gonadotropin secretion and response to GnRH in ovariectomized pony mares

In Exp. 1, 16 long-term ovariectomized pony mares were used to determine the effects of treatment with estradiol benzoate (EB) and dihydrotestosterone (DHT) benzoate alone, and in combination, on secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in daily blood samples and after three consecutive injections of gonadotropin releasing hormone (GnRH). Administration of EB alone, or in combination with DHT, every other day for 11 d reduced (P less than .05) concentrations of FSH and increased (P less than .05) concentrations of LH in daily blood samples, and increased (P less than .05) the secretion of both gonadotropins after administration of GnRH. Treatment with DHT alone had no effect (P greater than .10) on LH or FSH concentrations in daily blood samples and no effect on the LH response to exogenous GnRH. There was no interaction (P greater than .10) between DHT and EB treatment for any hormonal characteristic. In Exp. 2, the control mares and mares treated with DHT in Exp. 1 were equally allotted to treatment with vehicle or testosterone propionate (TP) every other day for six injections, and then GnRH was administered as in Exp. 1. Treatment with TP had no effect (P greater than .10) on LH or FSH concentrations in daily blood samples but increased (P less than .05) the FSH response to exogenous GnRH, confirming our findings in previous experiments. It is concluded that the TP-induced stimulation of FSH secretion after exogenous GnRH in ovariectomized mares may involve estrogens produced from aromatization of the injected androgen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of active immunization against estrogen on gonadotropin response to testosterone propionate treatment in ovariectomized pony mares

An experiment was conducted to determine whether partial neutralization of estrogens via active immunization alters testosterone propionate (TP)-induced increases in FSH secretion after GnRH administration in ovariectomized pony mares. Twenty mares were used in a 2 X 2 factorial arrangement of treatments (n = 5/group). Factor 1 was long-term active immunization against either bovine serum albumin (BSA) or estrone-17-oxime-BSA. Factor 2 was 11-d administration of either vehicle (vegetable oil) or TP (175 micrograms/kg BW). Plasma concentrations of FSH were not affected (P greater than .1) by either factor. As expected, the FSH response to exogenous GnRH was threefold greater (P less than .05) in BSA-immunized mares treated with TP than in BSA-immunized mares receiving oil. However, immunization against estrogens reduced (P less than .05) this TP-induced increase in FSH response by 52%. Plasma concentrations of LH were decreased (P less than .08) by TP; this effect was not altered (P greater than .1) by immunization against estrogen. The LH response to exogenous GnRH was not affected (P greater than .1) by either factor. We conclude that aromatization of testosterone to estrogen is partially responsible for the increased FSH response to exogenous GnRH in TP-treated mares. In contrast, suppression of LH concentrations by TP appears to involve only the androgenic effect of TP.     

Effects of dihydrotestosterone benzoate administration on gonadotropin secretion in ovariectomized pony mares

Eight long-term ovariectomized pony mares were treated with either dihydrotestosterone (DHT) benzoate (400 micrograms/kg body weight) in safflower oil or an equivalent amount of oil every other day for 21 d to determine the effects of DHT on follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations in blood samples drawn once daily and after administration of three successive injections of gonadotropin releasing hormone (GnRH). The GnRH injections were given at 4-h intervals on the day following the last DHT or oil injection. Treatment with DHT benzoate did not alter (P greater than .10) concentrations of FSH or LH in daily blood samples relative to controls. The FSH and LH response, assessed by areas under the GnRH curves, decreased (P less than .05) from the first to third injection of GnRH when averaged over both groups of mares. There was no effect of DHT treatment on FSH response to GnRH. There was an interaction (P less than .05) between treatment and GnRH injection for LH areas; areas decreased (P less than .05) for DHT-treated mares from the first to third GnRH injection but were unchanged for control mares. It seems that DHT alone cannot mimic the stimulatory effects of testosterone on FSH production and secretion as observed in previous experiments with ovariectomized and intact mares. Moreover, because intact mares have been shown previously to respond to DHT treatment with an increase in GnRH-induced FSH secretion, it appears that some mechanism is lost in long-term ovariectomized mares, making them unresponsive to DHT treatment.     

Contagious equine metritis: Antibody response of experimentally infected pony mares

Intrauterine inoculation of pony mares with the bacterium that is the causative agent of contagious equine metritis (CEM) resulted in clinical disease. A humoral immune response could be detected by agglutination and complement fixation (CF), and in some cases precipitating antibody was found by immunodiffusion tests. Agglutinating antibody was the most reliable serological indicator of overt infection and was detected in 8 of 28 mares after initial intrauterine inoculation of 3–4 × 10⁵ bacteria. Seventy percent of mares given a second inoculation and all mares given a third inoculation of 3–4 × 10⁵ bacteria produced detectable agglutinating antibody. Only two of five mares given the third inoculation developed detectable complement-fixing antibody. Only one mare showed evidence of reinfection after a second or third intrauterine inoculation. All of the mares given a single intrauterine inoculum of ≥ 8 × 10⁸ bacteria produced agglutinating antibody 10 to 30 days postinoculation (DPI) and 86% gave a positive CF test 10 to 20 DPI. Only mares with an agglutination titer of 320 or more produced precipitating antibody. Sera were considered positive in agglutination tests if they were reactive at a dilution of greater than 4 and positive in CF tests if they were reactive at a dilution of 4 or greater.Pony serum frozen at ?70°C was anticomplementary (AC). Treatment at 56°C abolished AC activity and revealed enhancing or procomplementary activity with guinea pig complement. Procomplementary activity could be abolished by treatment of heated pony serum with formaldehyde, which increased CF titers ≥ threefold in weakly reactive sera.     

Effects of dihydrotestosterone administration with and without estradiol pretreatment on gonadotropin secretion in ovariectomized pony mares

Twenty ovariectomized pony mares were used to determine if dihydrotestosterone propionate (DHTP) administration, with or without estradiol benzoate (EB) pretreatment, would have the same effects on follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion as testosterone propionate (TP) administration. All mares were given an initial injection of gonadotropin releasing hormone (GnRH) to characterize their LH and FSH response, and then two groups of mares (n = 4/group) were administered EB (22 micrograms/kg of body weight), two groups were administered vehicle (safflower oil) and a fifth group was administered TP (175 micrograms/kg of body weight) daily for 10 days. Following a second injection of GnRH, one group of EB-treated mares and one group of oil-treated mares were administered DHTP (175 micrograms/kg of body weight) daily for 10 days; the other EB- and oil-treated mares were administered oil and the TP-treated mares were continued on the same dose of TP for 10 days. A final injection of GnRH was then given. Treatment with EB increased (P less than .01) concentrations of LH in daily blood samples and increased (P less than .05) the LH response to exogenous GnRH. Administration of TP or DHTP reduced (P less than .05) both daily LH concentrations and the LH response to exogenous GnRH. Concentrations of FSH in daily blood samples were reduced (P less than .05) and the FSH response to exogenous GnRH was increased (P less than .05) by administration of EB alone, DHTP alone or TP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of phenolsulfonphthalein in horse and pony mares

Pharmacokinetics of phenolsulfonphthalein (PSP) in horse and pony mares was determined after injection of 1 mg/kg of body weight, IV. A plasma PSP concentration vs time curve was described adequately in horses and ponies by an open, 2-compartment model. There were significant differences in the elimination phase parameters, apparent volume of distribution at steady state, and apparent volume of distribution of horses and ponies. The harmonic mean elimination half-life of PSP in horses was significantly longer (P less than 0.001) than that in the ponies (16.4 and 10.0 minutes, respectively). The mean plasma clearance of PSP in horses was significantly (P less than 0.05) less than that in ponies (0.00554 and 0.00701 L/min/kg, respectively). There was no difference between horses and ponies in the metabolic clearance of PSP. The fraction of the administered dose of PSP excreted in the urine in the first 15 minutes was not significantly different between horses and ponies.     

Testosterone propionate effects on gonadotropin secretion in steers after administration of GnRH

Two experiments with steers were performed to determine the effects of 10 days of treatment with testosterone propionate (TP) on secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) after the administration of gonadotropin releasing hormone (GnRH). In Experiment 1, eight 15-month-old Holstein steers castrated at 12 months of age were used. In Experiment 2, eight beef-type steers between the ages of 12–18 months old and which had been castrated for 8–15 months were used. An initial injection of GnRH was followed by 10 daily injections of TP (175 ug/ kg of body weight) or safflower oil, and on the eleventh day a second injection of GnRH was given. Hormonal endpoints in long-term castrated steers (Experiment 2) were not altered by TP treatment. In contrast, TP treatment significantly suppressed FSH and LH concentrations in daily blood samples from Experiment 1 steers and significantly increased the response to GnRH. The lack of response in the long-term castrated steers (Experiment 2) to TP treatment is similar to the response observed in previous experiments with long-term ovariectomized cows. However, from the results of Experiment 1, it appears that the timing of castration influences the response to TP treatment.     

Cystometrography and urethral pressure profiles in healthy horse and pony mares

Cystometrography and urethral pressure evaluations were performed in 7 horse mares and 5 pony mares before and after sedation with xylazine. Before sedation, mean (+/- SD) maximal bladder contraction pressure was 91.4 +/- 16.5 cm of H2O in horses and was 86.0 +/- 14.4 cm of H2O in ponies, and maximal urethral closure pressure was 49.1 +/- 19.4 cm of H2O in horses and 37.7 +/- 14.4 cm of H2O in ponies. A significant difference was not found between values of nonsedated vs sedated animals. Only values for threshold volume were significantly different (P less than 0.05) between nonsedated horses (1,982 +/- 1,241 ml) and ponies (825 +/- 412 ml).     

Effects of active immunization against gonadotropin releasing hormone on gonadotropin secretion after ovariectomy and testosterone propionate administration to mares

Five lighthorse mares were actively immunized against gonadotropin releasing hormone (GnRH) conjugated to bovine serum albumin (BSA) to study the involvement of GnRH in luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion following ovariectomy (OVX) and after administration of testosterone propionate (TP). Five mares immunized against BSA served as controls. Immunizations were started on November 1, and OVX was performed in June (d 1). All mares were treated with TP from d 50 to 59 after OVX. On the day of OVX, concentrations of LH were lower (P less than .05) in GnRH-immunized mares than in BSA-immunized mares and were generally nondetectable; FSH concentrations were reduced (P less than .05) by 50% in GnRH-immunized mares relative to BSA-immunized mares. In contrast to BSA-immunized mares, plasma concentrations of LH or FSH did not increase after OVX in GnRH-immunized mares. The LH response to GnRH analog (less than .1% cross-reactive with GnRH antibodies) on d 50 was reduced (P less than .05) by 97% in GnRH-immunized mares relative to BSA-immunized mares, whereas the FSH response was similar for both groups. Treatment with TP for 10 d reduced (P less than .01) the LH response and increased (P less than .01) the FSH response to GnRH analog in BSA-immunized mares, but it had no effect (P greater than .1) on the response of either gonadotropin in GnRH-immunized mares.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endometrial and serum gentamicin concentrations in pony mares given repeated intrauterine infusions

Endometrial tissue and blood serum gentamicin (GT) concentrations were determined in 6 ovariectomized pony mares given intrauterine infusions (50 ml of a 5% commercial aqueous solution of GT) each day for 5 consecutive days. The mares were subjected to the following 3 treatments: (1) GT infusion only (trial A, control); (2) progesterone plus GT (trial B, P + G); and (3) estradiol plus GT (trial C, E + G). Endometrial tissue concentrations of GT (micrograms/g) at 24 and 120 hours were significantly higher (P less than 0.05) in trials B (65.54 +/- 15.57 and 100.33 +/- 19.27) and C (73.33 +/- 22.53 and 74.09 +/- 8.60) than in trial A (4.23 +/- 0.70). Endometrial concentration for trial A at 120 hours was also significantly higher than trial A at 24 hours. There was no significant difference (P greater than 0.05) in endometrial concentrations among trials A, B, and C at 120 hours. Serum GT concentrations were significantly lower than endometrial tissue concentrations. The highest serum concentrations of GT found in every trial occurred at 6 hours after each intrauterine infusion of GT. The highest overall serum concentration of GT (micrograms/ml) determined occurred in trial B (8.30 +/- 1.28) at 78 hours. There was no significant difference in serum concentrations of GT between days of treatment, except for trial A at 78 and 102 hours, respectively. Serum concentrations of GT were significantly higher (P less than 0.05) than trial A at 30, 54, 78, and 102 hours in trial B, and at 78 and 102 hours in trial C. There was no significant difference in serum concentrations of GT between trials B and C.     

Phenolsulfonphthalein pharmacokinetics and renal morphologic changes in adult pony mares with gentamicin-induced nephrotoxicosis

Changes in renal function, determined by pharmacokinetics of phenolsulfonphthalein (PSP), and renal morphologic features were examined in adult pony mares given 20 mg of gentamicin sulfate/kg of body weight, IV, q 8 h (group A) n = 7 or isotonic saline solution, IV, q 8 h, n = 5 (group B) for 14 days. Susceptibility of ponies to gentamicin-induced nephrotoxicosis was varied. Two group-A ponies developed acute renal failure and were euthanatized before treatment day 14, whereas 5 group-A A ponies did not develop physical or behavioral abnormalities after 14 days of gentamicin administration. All group-A ponies but none of group-B ponies developed ultrastructural abnormalities of the proximal tubular epithelium, consistent with gentamicin-induced nephrotoxicosis. Significant (P less than 0.05) differences were not detected in pharmacokinetic values of either group. Clearance of PSP was reduced in 4 group-A ponies that developed the most severe gentamicin-induced nephrotoxicosis. Changes in clearance of PSP were significantly (P less than 0.05) correlated with changes in the serum creatinine concentration.