0013-7227/91/1282-1065$03.00/0 Endocrinology Copyright © 1991 by The Endocrine Society
Vol. 128, No. 2 Printed in U.S.A.
Effects of Gonadal Steroids on Clearance of Growth Hormone at Steady State in the Rat* T. M. BADGER, W. J. MILLARDf, S. M. OWENS*, J. L A R O V E R E § , AND D. O'SULLIVANf Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and the Department of Pharmacodynamics, University of Florida College of Pharmacy, Gainesville, Florida 32610
ABSTRACT. Gonadal steroids have been implicated in the modulation of GH secretory patterns in the rat. We have studied the effects of testosterone (T) or estradiol (E2) on the steady state clearance (C1M) and plasma half-life (ti/2) of GH in male and female rats (n = 4-6/group). A femoral and a jugular cannula were surgically implanted into adult Sprague-Dawley rats. At the time of cannulation some rats were orchidectomized, and a Silastic capsule containing E2, T, or nothing was implanted sc. After recovery from surgery, either purified rat GH or a crude extract of rat pituitary was infused iv to attain steady state plasma GH concentrations. Blood samples were taken every 30 min for 4 h during the infusion, and nine samples were taken at 2.5-min intervals immediately after stopping the infusion. The mean Cl.. for GH in female rats was significantly (P < 0.001) less than that in males, whereas the ti /2 did not differ between the two groups. Neither the C1M nor the ti /2 was affected by
U
SING the chronically cannulated rat model, we and others have previously demonstrated that physiological GH secretion is both episodic and sex dependent (1-7). Adult male rats display a low frequency, high amplitude plasma pattern of GH secretion, whereas females exhibit a high frequency, low amplitude GH profile. Computer analysis of these GH secretory profiles indicate that females generally have twice as many plasma GH pulses than adult males, with individual pulses occurring approximately every hour in females and every 2.5-3 h in males. Furthermore, GH pulse amplitudes are generally 2-3 times greater in males than Received August 15,1990. Address all correspondence and requests for reprints to: Dr. Thomas M. Badger, Department of Pediatrics 512B, 4301 West Markham Street, Little Rock, Arkansas 72205. * This work was supported by Grants HD-22640 (to T.M.B.) and HD-22199 (to W.J.M.). t Present address: Department of Pharmacodynamics, Box J487, University of Florida College of Pharmacy, Gainesville, Florida 32610. % Present address: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 611, Little Rock, Arkansas 72205. Recipient of Research Scientist Development Award KO2-DA-00110 from the NIDA. § Present address: Department of Pediatrics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 512B, Little Rock, Arkansas 72205.
castration in males or females. The C1M of GH in E2-treated castrated males was significantly less (P < 0.001) than that for intact males, but the ti/2 did not differ between the two groups. The C1M for GH was greater in T-treated ovariectomized rats than in intact females, but the ti/2 did not differ with T treatment. These results suggest that 1) the C1M for GH is lower in female rats than in males; 2) 4 weeks of gonadectomy has no effect on the C1M in males or females; 3) under experimental conditions, E2 decreases and T increases the C1M for GH; and 4) the ti/2 for GH is not different in males or females. The steroidinduced changes in Cl8fl in the absence of detectable effects on ti/2 suggest that factors affecting the volume of distribution at steady state (i.e. plasma GH-binding proteins or GH heterogeneity) are involved in the effects of gonadal steroids on GH clearance in the rat. (Endocrinology 128: 1065-1072,1991)
in females. Characteristic of the masculine GH secretory profile is the prolonged interpulse interval of GH secretion where circulating GH levels remain at or below the assay sensitivity (
Vol. 128, No. 2 Printed in U.S.A.
Effects of Gonadal Steroids on Clearance of Growth Hormone at Steady State in the Rat* T. M. BADGER, W. J. MILLARDf, S. M. OWENS*, J. L A R O V E R E § , AND D. O'SULLIVANf Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and the Department of Pharmacodynamics, University of Florida College of Pharmacy, Gainesville, Florida 32610
ABSTRACT. Gonadal steroids have been implicated in the modulation of GH secretory patterns in the rat. We have studied the effects of testosterone (T) or estradiol (E2) on the steady state clearance (C1M) and plasma half-life (ti/2) of GH in male and female rats (n = 4-6/group). A femoral and a jugular cannula were surgically implanted into adult Sprague-Dawley rats. At the time of cannulation some rats were orchidectomized, and a Silastic capsule containing E2, T, or nothing was implanted sc. After recovery from surgery, either purified rat GH or a crude extract of rat pituitary was infused iv to attain steady state plasma GH concentrations. Blood samples were taken every 30 min for 4 h during the infusion, and nine samples were taken at 2.5-min intervals immediately after stopping the infusion. The mean Cl.. for GH in female rats was significantly (P < 0.001) less than that in males, whereas the ti /2 did not differ between the two groups. Neither the C1M nor the ti /2 was affected by
U
SING the chronically cannulated rat model, we and others have previously demonstrated that physiological GH secretion is both episodic and sex dependent (1-7). Adult male rats display a low frequency, high amplitude plasma pattern of GH secretion, whereas females exhibit a high frequency, low amplitude GH profile. Computer analysis of these GH secretory profiles indicate that females generally have twice as many plasma GH pulses than adult males, with individual pulses occurring approximately every hour in females and every 2.5-3 h in males. Furthermore, GH pulse amplitudes are generally 2-3 times greater in males than Received August 15,1990. Address all correspondence and requests for reprints to: Dr. Thomas M. Badger, Department of Pediatrics 512B, 4301 West Markham Street, Little Rock, Arkansas 72205. * This work was supported by Grants HD-22640 (to T.M.B.) and HD-22199 (to W.J.M.). t Present address: Department of Pharmacodynamics, Box J487, University of Florida College of Pharmacy, Gainesville, Florida 32610. % Present address: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 611, Little Rock, Arkansas 72205. Recipient of Research Scientist Development Award KO2-DA-00110 from the NIDA. § Present address: Department of Pediatrics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 512B, Little Rock, Arkansas 72205.
castration in males or females. The C1M of GH in E2-treated castrated males was significantly less (P < 0.001) than that for intact males, but the ti/2 did not differ between the two groups. The C1M for GH was greater in T-treated ovariectomized rats than in intact females, but the ti/2 did not differ with T treatment. These results suggest that 1) the C1M for GH is lower in female rats than in males; 2) 4 weeks of gonadectomy has no effect on the C1M in males or females; 3) under experimental conditions, E2 decreases and T increases the C1M for GH; and 4) the ti/2 for GH is not different in males or females. The steroidinduced changes in Cl8fl in the absence of detectable effects on ti/2 suggest that factors affecting the volume of distribution at steady state (i.e. plasma GH-binding proteins or GH heterogeneity) are involved in the effects of gonadal steroids on GH clearance in the rat. (Endocrinology 128: 1065-1072,1991)
in females. Characteristic of the masculine GH secretory profile is the prolonged interpulse interval of GH secretion where circulating GH levels remain at or below the assay sensitivity (
