Short-term inhibition of prolactin secretion by naloxone treatment in the pregnant gilt

Animal Reproduction

Science39 ( 1995) 59-69

Short-term inhibition of prolactin secretion by naloxone treatment in the pregnant gilt* Bozena Department

Szafranska’,

James E. Tilton”

of Animal and Range Sciences, North Dakota State Universily, Fargo, ND 58105-5727,

USA

Accepted 5 January 1993

Abstract

The involvement of endogenous opioids in modulation of prolactin (PRL) secretion during pregnancy in the pig was studied. Twenty-four crossbred pregnant gilts ( 150 f 10 kg) were cannulated via the cephalic vein 24-48 h before treatment with 1 mg kg-’ body weight of naloxone (NAL) or 3 ml of saline (CONT) i.v. at Day 40 (NAL, n = 6; CONT, n = 6) or Day 70 (NAL, n = 6; CONT, n=6) of pregnancy. Blood plasma was collected at 15 min intervals from 1 h before to 3 h after treatment with NAL or saline. At Day 40 of pregnancy, administration of NAL caused a decrease in mean plasma PRL concentrations at 60 min, 120 min and 180 min post-treatment (NAL, 19.1 + 1.3 14.6+0.7ngml-‘,P 0.05) between groups in this stage of gestation. Mean concentrations of progesterone were similar during the pre- and post-treatment periods in both stages of pregnancy. These data would suggest a possible role of the opioids in modulation of PRL secretion at these stages of pregnancy in the pig. Keywords: Pig; Pregnancy;

Naloxone; Prolactin; Estradiol; Progesterone

Published with the approval of the Director of the Agricultural Experiment Station as Journal Article No. 2205. and Technology, Department of Animal Physiology, lo-718 Olsztyn-Kortowo, Poland. * Corresponding author. ??

I Permanent address: University of Agriculture

0378-4320/95/$09.50 0 1995 Elsevier Science B.V. All rights reserved SSDIO378-4320(95)01381-4

60

B. Szafranska, J.E. Tilton /Animal Reproduction Science 39 (1995) 59-69

1. Introduction

Endogenous opioid peptides (EOP) have been found to be involved in modulation of prolactin (PRL) secretion in several species: rats (Penerai et al., 1985; Yogev et al., 1985; Enjalbert et al., 1990), sheep (McMillen and Deayton, 1989; Malven et al., 1990)) heifers (Leshin et al., 1990), pigs (Barb et al., 1985, 1986, 1991; Armstrong et al., 1988a,b, 1990; Okrasa et al., 1990)) monkeys (Wardlaw and Ferin, 1990) and humans (Benker et al., 1990; Marlettini et al., 1990). The regulatory mechanisms of PRL secretion under EOP influence are not completely elucidated in the pig and only slight attention has been given to the involvement of EOP in PRL secretion during pregnancy in any species. Changes in EOP receptors in the rat uterus during pregnancy (Genazzani et al., 1984; Baraldi et al., 1985), the presence of EOP receptors in the hypothalamus of ovine fetus (Yang and Challis, 1991), the existence of opioid modulation of PRL secretion in pregnant sheep (McMillen and Deayton, 1989) and the occurrence of EOP in porcine uterine fluid and endometrial extracts (Li et al., 1987, 1991) suggests the functional involvement of opioids in a modulatory role during pregnancy. However, other investigators (Du Mesnil du Buisson and Denamur, 1969; Rolland et al,, 1976; Bazer and First, 1983; Li et al., 1989) and our previous reports (Szafranska and Ziecik, 1990; Szafranska and Tilton, 1993a) suggested a luteotrophic role of PRL in pregnancy maintenance in the pig. Our objective was to establish the influence on PRL secretion of an EOP antagonist during pregnancy in the pig. Days 40 and 70 were chosen because of observed differences in hormonal activity indicated in the above mentioned reports and our previous studies.

2. Materials and methods 2.1. Animals and blood sampling sequence Twenty-four pregnant Duroc X Yorkshire crossbred gilts ( 150 + 10 kg) mated at second estrus were used in two experiments conducted on Day 40 (naloxone (NAL), n = 6; saline (CONT),n = 6) and 70 (NAL, n = 6; CONT, n = 6) of pregnancy. An indwelling cannula was surgically implanted into the jugular vein via the cephalic vein 24-48 h before treatment.

Blood samples (5 ml) were collected every 15 min from 1 h before to 3 h after treatment with NAL. The plasma was removed and stored at - 20°C until assayed for PRL, estradiol and progesterone concentrations. Prolactin was quantified in all samples, whereas progesterone and estradiol were determined in hourly samples only. 2.2. Treatment Naloxone (Sigma Chemical Co., St Louis, MO) was administered intravenously in 3 ml saline at a dosage of 1 mg kg-’ body weight. The controls received 3 ml of saline on Days 40 and 70 of pregnancy. Treatments were administered immediately before 09:OO h.

B. Szafranska, J. E. Tilton /Animal Reproduction Science 39 (I 995) 59-69

61

2.3. Radioimmunoassays Plasma PRL concentrations were determined in duplicate 100 ~1 aliquots by double antibody radioimmunoassay (Dusza and Krzymowska, 1979). Porcine PRL (pPRL-KK3, provided by Dr K. Kochman, Jablonna, Poland) was used for chloramine iodination and as standards. Primary antibodies from goats immunized against porcine PRL (Research Products, Mt. Prospect, IL) were used in a titer of 150 000. Commercially prepared second antibodies (Goat IgG Antiserum, Sigma) against immunoglobulin of goats were obtained from immunized donkey, and used in a 15 dilution. Sensitivity of the assay was 0.12 ng ml-‘. Intra- and interassay coefficients of variation were 2.6% and 8.1%, respectively. Estradiol was determined in duplicate 500 ~1 aliquots by utilizing standard extraction methods (Hotchkiss et al., 1971) with ethyl ether and with the primary antibodies from immunized rabbits against a conjugate of 17-estradiol-6-CMO:BSA (B. Szafranska and A. Ziecik, unpublished data, 1989) and with [ 2,4,6,7-“H] -estradiol (DuPont NEN Products, Boston, MA) as a tracer. The cross-reactions of antiserum were: estrone, 0.58%, and less than 0.01% for 5a-androstane-3,17-dione, androsterone, epiandrosterone and testosterone. No cross-reactions were observed with 5a-pregnan-3a-ol-20-one, 5cY-pregnan-3P-ol-20one, progesterone, 4-pregnen-20@-ol-3-one, 4-pregnen-20/J-ol-3-one, S/3-androstane-3a17P-dione, 5p-androstane-3a-17P-diol, 4-androstan-1 lp-01-3, 17-dione, 5cw-androstan17/?-ol-3-one. This antibody has been determined to have an affinity constant of 1.0X 10”’ 1 mall’ by Scatchard analysis. The antiserum was used in a titer of 1:30 000. Recovery of estradiol in extracted samples was 88 f 2% and final values were corrected for these losses. Intra- and interassay coefficients of variation were 3.5% and 5.3%, respectively with the sensitivity of the assay being 1 pg mll ‘. Progesterone was determined in duplicate 100 ~1 aliquots by utilizing the direct assay in plasma coat-a-count procedure (Diagnostic Products Co., Los Angeles, CA). Sensitivity of the assay was 0.1 ng ml- ‘, Intra- and interassay coefficients of variation were 4.6% and 5.0%, respectively. 2.4. Statistical analyses Prolactin and estradiol concentrations were analyzed by split plot in time analysis of variance (Gill and Hafs, 1971), where stage of pregnancy, treatment and time were the main factors. Sampling time at Days 40 and 70 of pregnancy were divided into four l-h periods. The first hourly period represented the mean of PRL concentrations for all animals prior to treatment. The data before and after treatment were analyzed separately for each time of sampling and period of treatment and then compared with the control group during the comparable periods. Mean comparisons of prolactin and estradiol concentration were accomplished with Duncan’s multiple range test and differences between progesterone means within a time period were analyzed by Student’s t-test.

3. Results Concentrations of PRL during both periods of pregnancy were generally higher than in our previous long-term studies. At Day 40, mean plasma PRL concentrations across groups

B. Szafranska, J.E. Tilton / Animal Reproduction Science 39 (1995) 59-49

62

40 t

0 35 -

NAL

NAL

ACONT

30 -

0”““““““” oeoo

0900

1100

loo0 Time

Fig. 1. Mean concentrations (ng XII-‘) of PRL before and after treatment with NAL on Day 40 of pregnancy. Mean post-treatment SEM was If:0.75 for NAL (n = 6) and f 0.37 for the CONT group (n = 6) : *P < 0.05; ***P
60

2 o 50 s 40 30 0800

0900

1000

1100

1200

Time Fig. 2. Percentage change in PRL profiles for NAL groups before and after treatment with NAL on Days 40 and 70 relative to the CONT groups during both periods of pEgnancy.

B. Szafranska,

Table 1 Mean progesterone pregnancy

concentration

n

.I. E. Tilton /Animal

Science 39 (1995) 59-69

63

’) before and after treatment with NAL on Days 40 and 70 of

f SEM (ng ml-

Pretreatmenta

Reproduction

Time post-treatment

(min)

+60

+ 120

+180

xfSEM

16.6 * 0.9 14.9rtO.8

15.1 kO.8 14.3* 1.1

14.3 * 0.9 13.2kO.8

15.3 +0.8 14.2f0.9

14.8 + 0.7 14.2 f 0.6

13.4*0.7 14.0*0.7

13.9 k0.8 13.4 kO.8

14.1 kO.7 13.9kO.7

Day 40

Cont NAL

6 6

15.9kO.8 14.7 + 0.9

x+SEM

15.3+0.8

Day 70

Cont NAL

6 6

14.9 f 0.8 13.9+0.7

x+SEM

14.4 rt 0.8

%ixty minutes prior to treatment.

Table 2 Mean estradiol concentration Period

f SEM (pg ml- ‘) after treatment with NAL on Days 40 and 70 of pregnancy Day 70

Day 40

+lh +2h +3h

NAL (n=6)

Saline (n=6)

NAL (n=6)

Saline (n=6)

19.8 k4.8 27.1 &6.8a 25.8k7.6a

9.5* 1.5 7.6fl.Ob 6.6 f 0.8b

29.5 f 3.4 25.4 k4.2 25.2 i-4.8

14.9*4.1 18.9+ 1.7 17.3 f 3.4

Means within rows followed by different letters are significantly

Table 3 Split-plot analysis of plasma prolactin concentrations treatment

different (P
as affected by stage of pregnancy,

treatment and time post-

Source

d.f.

Mean square

F

PC F) > FM

(a) Stage of pregnancy Error (b) Treatment

1 5 1 1 10 15 15 15 15 300

4278.7 2665.7 10155.9 2042.4 1574.6 240.2 65.3 34.8 13.2 37.9

1.61

0.7290

6.45 1.3

0.0284* 0.7165

6.42 1.72 0.92 0.35

o.ooo*** 0.0461** 0.5463 0.9890

(a) x(b) Error (c) Time (a) X (c) (b) x(c) (a) X (b) X (c) Error *p
**p
***P
B. Szafransku, J.E. Tilton /Animal Reproduction Science 39 (1995) 59-49

64

Table 4 Split-plot analyses of plasma estradiol concentrations as affected by stage of pregnancy, treatment and time posttreatment Source

d.f.

(a) Stage of pregnancy Error (b) Treatment (a) X(b) Error (c) Time (a) X (c) (b) X (c) (a) X (b) X (c) Error

5 1 1 10 2 2 2 2 40

1

Mean squares 605.8 274.3 3043.3 202.2 201.4 11.2 13.5 1.9 136.1 41.3

F

2.2

P(F) > FM,

0.7893

15.11 1.oo

0.0031** 0.6583

0.27 0.33 0.05 3.29

0.2368 0.2771 0.0449* 0.0465*

*p
were 21.8 + 1.6 ng ml- ’during the pre-treatment period (Fig. 1). Administration of NAL caused a decrease in mean plasma PRL concentrations at 60 min, 120 min and 180 min post-treatment(19.1f1.3ngml-‘,P<0.05; 15.8f0.6ngml-‘,P
35

30

e-25

E 2

220 0" 15 I-10

0

0900

1000

1100

Time Fig. 3. Mean concentrations (ng ml-‘) of PRL before and after treatment with NAL on Day 70 of pregnancy. Mean post-treatment SEM was f 0.84 for NAL (n = 6) and f 0.94 for the CONT (n = 6) group.

B. Szafranska, J.E. Tilton / Animal Reproduction Science 39 (1995) 5949

65

At Day 70, mean plasma PRL concentrations in all gilts were 32.9 k 1.4 ng ml- ’during the pre-treatment period. Infusion of NAL at this stage of pregnancy also decreased (P < 0.001) plasma PRL concentrations at 60 min, 120 min and 180 min after treatment (20.1+ 1.6 ng ml-‘, 16.2+ 1.5 ng ml-’ and 14.8*0.4 ng ml-‘, respectively) compared with the CONT group (33.4f 1.7 ng ml-‘, 34.1* 1.3 ng ml-’ and 29.1 f0.9 ng ml-‘, respectively). These values represented approximately 40-50% of control PRL concentrations by 3 h after treatment (Fig. 2). Plasma progesterone and estradiol concentrations were not altered at this stage of pregnancy (Tables 1 and 2). Split-plot analyses indicated that treatment with NAL (P < 0.05) and time after treatment (P < 0.001) affected plasma prolactin concentrations but stage of pregnancy was not a major influence (Table 3). Analyses of plasma estradiol concentrations indicated that NAL treatment influenced (P < 0.05) its secretion at Day 40 (Table 4).

4. Discussion Our results demonstrated that the inhibition of prolactin secretion could be caused by naloxone administration on Days 40 and 70 of pregnancy, indicating the existence of an opiate-sensitive PRL control during gestation (Figs. l-3, Table 3). Slightly higher PRL concentrations occurred during these short-term studies than were found in our previous long-term experiments (Szafranska and Tilton, 1993a) and may be related to post-surgical stress. However, 60-70% decreases of plasma PRL concentration were observed after NAL treatment (Fig. 2). Our results are in agreement with the studies performed in pregnant ewes (McMillen and Deayton, 1989), in which decreased prolactin concentrations in maternal circulation after naloxone infusion during late gestation were reported. Moreover, intraventricular administration of morphine resulted in an increase of PRL secretion in ovariectomized gilts (Estienne et al., 1990). In contrast, peripherally administered morphine inhibited PRL secretion in postpartum sows (Armstrong et al., 1988a). Blocking EOP receptors in the gilt at various physiological states by administration of NAL resulted in observable differences in plasma PRL concentrations. Luteal phase NAL treatments of cycling gilts (Barb et al., 1985,1986) caused plasma PRL increases. However, NAL did not affect PRL concentration during the follicular phase of the estrous cycle or after ovariectomy (Barb et al., 1986) but decreased PRL concentrations during the late follicular phase (Okrasa et al., 1990) and during lactation (Armstrong et al., 1988b, 1990; Mattioli et al., 1986). The role of EOP in prolactin secretion has been shown to be mediated mainly via hypothalamic neurotransmitters: dopamine (DA) and serotonin (5-HT) (Benker et al., 1990). In most cases, naloxone (Ngai et al., 1976), the EOP receptor antagonist, decreases basal circulating PRL concentrations. It is not clear in pigs whether NAL increases hypothalamic DA or decreases 5-HT activity. Beta-endorphin is the principal and most potent EOP for elevating serum PRL concentrations (Ragavan and Franz, 198 1). Demonstration of proopiomelanocortin immunostaining, as a Pendorphin precursor in the pig hypothalamus (Kineman et al., 1989) provides evidence that EOP are involved in this regulatory mechanism. However, in porcine pituitaries both leu-enkephalins (Goldstein et al., 198 1) and dynorphins (Fischli et al., 1982) have been found. Prolactin release appears to be

66

B. Szafranska, J. E. Tilton /Animal Reproduction Science 39 (I 995) 59-69

activated through the mpl and rnp2 receptors for EOP (Koenig and Krulich, 1984) and their subtypes (Haynes et al., 1989). The tuberoinfundibular dopaminergic neurons of the arcuate nucleus (Weiland and Wise, 1989; Loose et al., 1990) and tuberohypophyseal dopaminergic nerves terminals are directly influenced through EOP or by changes in density of EOP receptors on dopaminergic neurons (Garris and Ben-Jonathan, 1990). However, histamine (HA), as a hypothalamic neurotransmitter, may have a tonic effect on the basal PRL secretion that is involved in the mediation of stress-induced release of PRL. Because of that, HA involvement cannot be excluded from these EOP effects. Infusing histamine either intracerebroventricularly, or systemically stimulates PRL secretion in a dose-dependent fashion (Knigge, 1990). The PRL stimulatory effect of HA is mediated partly via an inhibition of the tuberoinfundibular dopaminergic system and partly via an activation of the serotoninergic system. However, in the mediation of PRL response, HA and DA may be involved via other EOP forms not yet elucidated. Schally et al. ( 1991) isolated and purified two peptides from porcine hypothalami with in vitro prolactin releaseinhibiting activity. One was found to be identical in amino acid sequence to residues 2752 of the N-terminal fragment of the proopiomelanocortin precursor protein. Moreover, Sinha et al. ( 199 1) found four forms of glycosylated prolactin in the pig, immunologically and biologically different, with 10, 40 or 60% activity of total nonglycosylated prolactin. Both forms, glycosylated and nonglycosylated, are completely necessary to achieve biological effects of total PRL (Young et al., 1990). Apparently, different physiological states of reproduction are controlled by more than one mechanism, through which EOP, with heterogeneity of neurons (Tiligada and Wilson, 1990) can have their influence on regulation of heterogeneous PRL secretion. Available evidence about EOP and their effect on PRL release at different stages of reproduction demonstrated that these mechanisms are controlled by circulating steroid hormones. Estrogens are one of the most potent stimulators of PRL cells. Prolonged estrogen administration induced PRL cell hyperplasia and increased pituitary weights in the rat as well as elevating serum PRL concentrations (Stefaneanu and Kovacs, 1991). In pigs, pituitary gland weight increases 50% during pregnancy compared with that in non-pregnant same-age controls (Anderson and Melampy, 1967) and likely results from endogenous estrogen. In our study, estradiol concentration was enhanced on Day 40 of pregnancy. We can only suggest that it was caused by blocked EOP receptors and/or lower concentrations of PRL; however, we determined increased luteinizing hormone concentrations at this stage of pregnancy (Szafranska et al., 1991). It is also difficult to explain whether this estradiol increase was caused by increased secretion from the maternal or fetal unit. Marlettini et al. (1990) demonstrated that placental estrogens during human pregnancy stimulate both the maternal and fetal hypophysis and their PRL secretions. Steroids can be involved in this mechanism in several areas. Garris and Ben-Jonathan (1991) presented a model of the proposed mechanism by which estradiol stimulates DA release from the posterior pituitary. In this model, estradiol decreased tonic inhibition by P-endorphin from the intermediate lobe and DA release from the neural lobe. Estradiol can convert P-endorphin into an inactive form or decrease the release of P-endorphin. In conclusion, the inhibition of EOP receptors appeared to decrease the secretion of PRL on Days 40 and 70 of pregnancy in the pig. On the basis of our results and several other papers, we hypothesize that during pregnancy, PRL concentration is relatively low because

B. Szafranska, J.E. Tilton /Animal Reproduction Science 39 (1995) 59-69

67

of an elevated secretion of DA. This secretion, modulated by EOP action, is enhanced during late pregnancy, when estradiol is also increased. Treatment with NAL modulated the concentration of PRL to a greater extent on Day 70 than Day 40 of pregnancy, suggesting changes in EOP involvement during late gestation in this species. The involvement of opioids in this regulatory mechanism(s) may be altered by intracellular calcium distribution within the porcine anterior pituitary cells (Szafranska et al., 1993b).

Acknowledgments The authors are grateful for the technical assistance of Robert Weigl in the preparation for surgery, blood sampling and radioimmunoassays, and Dr. Dariusz Golonka for statistical assistance. We wish to thank Ron Zimprich for the provision of the animals, Tim Johnson and Terry Skunberg and the staff of the Small Animal Research Center for their care of animals and help during the experiments and Dave Zaeske, from the Meats Laboratory, for slaughter of the animals.

References Anderson, L.L. and Melampy, R.M., 1967. Hypophysial and uterine influences on pigs luteal function. In: GE. Lamming and E.C. Amoroso (Editors), Reproduction in the Female Mammal. Butterworths, London, pp. 28.5-3 16. Armstrong, J.D., Kraeling, R.R. and Britt, J.H., 1988a. Morphine suppresses LH concentrations in transiently weaned sows and delays onset of estrus after weaning. J. Anim. Sci., 66: 2216-2223. Armstrong, J.D., Kraeling, R.R. and Britt, J.H., 1988b. Effects of naloxone or transient weaning on secretion of LH and prolactin in lactating sows. J. Reprod. Fertil., 83: 301-308. Armstrong, J.D., Esbenshade, K.L., Coffey, M.T., Heimer, E., Campbell, R., Mowles, T. and Felix, A.. 1990. Opioid control of growth hormone in the suckled sow is primarily mediated through growth hormone releasing factor. Dom. Anim. Endocrinol., 7: 191-198. Baraldi M., Giarre, G., Santi, M., Facchinetti, F., Petraglia, F. and Genazani, A.R., 1985. Pregnancy related changes of opiate receptors identified in rat uterine membranes by ‘H-naloxone binding. Peptides, 6: 971-974. Barb, C.R., Kraeling, R.R., Rampacek, G.B. and Whisnant, C.S., 1985. Opioid inhibition stimulates luteinizing hormone and prolactin secretion in the pig. Dom. Anim. Endocrinol., 2: 93-98. Barb, CR., Kraeling, R.R., Rampacek, G.B. and Whisnant, C.S., 1986. Influence of stage of estrous cycle on endogenous opioids modulation of luteinizing hormone, prolactin, and cortisol secretion. Biol. Reprod., 35: 1162-I 167. Barb, C.R., Kraehng, R.R. and Rampacek, G.B., 1991. Opioid modulation ofgonadotropin and prolactin secretion in domestic farm animals. Dom. Anim. Endocrinol., 8: 15-27. Bazer, F.W. and First, N.L., 1983. Pregnancy and parturition. J. Anim. Sci., 57: 425-460. Benker, G., Jaspers, C., Hausler, G. and Reinwein, D., 1990. Control of prolactin secretion. Klin. Wochenschr., 68: 1157-l 167. Du Mesnil du Buisson, F. and Denamur, R., 1969. Mechanismes du controle de la fonction luteale chez la truie, la brebis et la vache. Int. Congr. Ser. Excerpta Med., 184: 927-934. Dusza, L. and Krzymowska, H., 1979. Plasma prolactin concentration during the oestrous cycle of sows. J. Reprod. Fertil., 57: 5 1l-5 14.

68

B. Szafranska. LE. Tilton /Animal Reproduction Science 39 (1995) 59-69

Enjalbert, A., Israel, J.M., Zhang, J., Kordon, C. and Vincent, J.D., 1990. Interaction of opiate peptides with dopamine effects on prolactin secretion and membrane electrical properties in anterior pituitary cells from lactating rats. J. Neuroendocrinol., 2: 807-813. Estienne, M.J., Kesner, J.S., Barb, R.C., Kraeling, R.R. and Rampacek, GE., 1990. Gonadotropin and prolactin secretion following intraventricular administration of morphine in gilts. Proc. Sot. Exp. Biol. Med., 193: 9297. Fischli, W., Goldstein, A., Hunkapiller, M.W. and Hood, L., 1982. Isolation and amino-acid sequence analysis of a 4000 dalton dynorphin from porcine pituitary. Proc. Natl. Acad. Sci. USA, 79: 5435-5437. Garris, P.A. and Ben-Jonathan, N., 1990. Regulation of dopamine release in vitro from the posterior pituitary by opioid peptides. Neuroendocrinology, 52: 399-404. Garris, P.A. and Ben-Jonathan, N., 1991. Estradiol rapidly stimulates dopamine release from the posterior pituitary in vitro. Neuroendocrinology, 53: 601-607. Genazzani, A.R., Petraglia, F., Ficchinetti, F., Volge, A., Giarre, G., Santi, M. and Baraldi, M., 1984. Central, peripheral, and placental opioids in pregnancy. In: Opioid Modulation of Endocrine Function. New York, pp. 237-246. Gill, J.L. and Hafs, H.D., 1971. Analysis of repeated measurements of animals. J. Anim. Sci., 33: 331-336. Goldstein, A., Fischli, W., Lowney, L.I., Hunkapiller, M.W. and Hood, L., 1981. Porcine pituitary dynorphin: complete amino-acid sequence of the biologically active heptadecapeptide. Proc. Natl. Acad. Sci. USA, 76: 7219-7223. Haynes, N.B., Lamming, G.E., Yang, K.P., Brooks, A.N. and Finnie, A.D., 1989. Endogenous opioid peptides and farm animal reproduction. In: S.R. Milligan (Editor), Oxford Reviews of Reproductive Biology, Vol. II, pp. 111-145. Hot&kiss, J., Atkinson, L.E. and Knobil, E., 1971. Time course of serum estrogen and luteinizing hormone concentration during the menstrual cycle of the rhesus monkey. Endocrinology, 89: 177-183. Kineman, R.D., Kraeling, R.R., Grim, J.W., Leshin, L.S., Barb, C.R. and Rampacek, G.B., 1989. Localization of proopiomelanocortin (POMC) immunoreactive neurons in the forebrain of the pig. Biol. Reprod., 40: 11191126. Knigge, U.P., 1990. Histaminergic regulation of prolactin secretion. Danish Med. Bull., 37: 109-124. Koenig, J.I. and Krulich, L., 1984. Differential role of multiple opioid receptors in the regulation of secretion of prolactin and growth hormone in rats. In: Opioid Modulation of Endocrine Function. New York, pp. 89-98. Leshin, L.S., Rund, L.A., Thompson, F.N., Mahaffey, M.B., Chang, W.J., Byerly, D.J. and Kiser, T.E., 1990. Serum prolactin and growth hormone responses to naloxone and intracerebral ventricle morphine administration in heifers. J. Anim. Sci., 68: 1656-1665. Li, W.I., Chen, C.L., Hansen, P.J. and Bazer, F.W., 1987. PEndorphin in uterine secretions of pseudopregnant and ovariectomized, ovarian steroid-treated gilts. Endocrinology, 121: 111l-l 115. Li, WI., Sung, L.C. and Bazer, F.W., 1991. Immunomactive methionine-enkephalin secretion by porcine uterus. Endocrinology, 128: 21-26. Li, Y., Molina, J.R., Klindt, J., Bolt, D.J., Anderson, L.L., 1989. Prolactin maintains relaxin and progesterone secretion by aging corpora lutea after hypophysial stalk transection or hypophysectomy in the pig. Endocrinology, 124: 1294-1304. Loose, M.D., Ronnekleiv, O.K. and Kelly, M.J., 1990. Membrane properties and response to opioids of identified dopamine neurons in the guinea pig hypothalamus. J. Neurosci., lO( 11): 3627-3634. Malven, P.V., Stanisiewski, E.P. and Haglof, .%A., 1990. Ovine brain areas sensitive to naloxone-induced stimulation of luteinizing hormone release. Neuroendocrinology, 52: 373-38 1. Marlettini, M.G., Cassani, A., Morselli-Labate, A.M., Crippa, S., Contarini, A., Miniero, R., Plate, L. and Orlandi, C., 1990. Maternal and fetal prolactin in pregnancy-induced hypertension. Arch. Gynecol. Obstet., 247: 7381. Mattioli, M., Conte, F., Gabeati, G. and Seren, E., 1986. Effect of naloxone on plasma concentrations of prolactin and LH in lactating sows. J. Reprod. Fertil., 76: 167-173. McMillen, I.C. and Deayton, J.M., 1989. Effect of morphine and naloxone on plasma prolactin concentrations in the fetal sheep and pregnant ewe during late gestation. Neuroendocrinology, 49: 286-290. Ngai, S.H., Berkowitz, B.A., Yang, J.C., Hempstead, J. and Spector, S., 1976. Pharmacokinetics of naloxone in rats and man: basis for its potency and short duration of action. Anesthesiology, 44: 398-401. Okrasa, S., Weigl, R., Mah, J. and Tilton, J., 1990. Concentration of prolactin, LH and FSH after naloxone administration in follicular phase gilts. Anim. Reprod. Sci., 22: 3946.

B. Szafranska, J.E. Tilton /Animal

Reproduction Science 39 (1995) 59-69

69

Penerai, A.E., Petraglia, F., Sacerdote, P. and Genazzani, A.R., 1985. Mainly rnp opiate receptors ate involved in luteinizing hormone and prolactin secretion. Endocrinology, 117: 1096-1099. Ragavan, V.V. and Franz, A.G., 1981. Opioid regulation of prolactin secretion: evidence for specific role of pendorphin. Endocrinology, 109: 1769-177 1. Rolland, R., Gunsalus, G.L. and Hammond, J.M., 1976. Demonstration of specific binding of prolactin by porcine corpora lutea. Endocrinology, 98: 1083-1091. Schally, A.V., Guoth, J.G., Redding, T.W., Groot, K., Rodriguez, H., Szonyi, E., Stults, J. and Nikolics, K., 1991. Isolation and characterization of two peptides with prolactin release-inhibiting activity from porcine hypothalami. Proc. Natl. Acad. Sci. USA, 88: 3540-3544. Sinha, Y.N., DePaolo,L.V., Haro,L.S., Singh, R.N.P.. Jacobsen, B.P., Scott, K.E. andLewis, U.J., 1991. Isolation and biochemical properties of four forms of glycosylated porcine prolactin. Mol. Cell. Endocrinol., 80: 203213. Stefaneanu, L. and Kovacs, K., 1991. Effects of drugs on pituitary fine structure in laboratory animals. J. Electron. Microsc. Techniques, 19: 80-89. Szafranska, B. and Ziecik, A., 1990. Effect of bromocriptine administration on maintenance of late pregnancy in the pig. Exp. Clin. Endocrinol., 96: 321-324. Szafranska, B ., Weigl, R.M. and Tilton, I.E., 199 I. Effect of opioid inhibition on luteinizing hormone concentration in the pregnant pig. J. Anim. Sci., 69 (Suppl. 1): 4 18. Szafranska, B. and Tilton, J.E., 1993a. Prolactin as a luteotropin during late pregnancy in the pig. J. Reprod. Fertil., 98: 643-648. Szafranska, B., Ary, T. and Tilton, J.E., 1993b. Kinetics of intracellular calcium in single anterior pituitary cells with opioid-sensitivity. 3rd Int. Pituitary Congress, Marina Del Rey, California, 13-15 June, Abstract MP-I 3. Tiligada, E. and Wilson, J.F., 1990. Minireview-Ionic, neuronal and endocrine influences on the proopiomelanocortin system of the hypothalamus. Life Sci., 46: 8 I-90. Wardlaw, S.L. and Ferin, M., 1990. Interaction between P-endorphin and cr-melanocyte-stimulating hormone in the control of prolactin and luteinizing hormone secretion in the primate. Endocrinology, 126: 2035-2040. Weiland, N. and Wise, P.M., 1989. Hyperprolactinemia decreases naloxone binding in the arcuate nucleus of ovariectomized rats. Neuroendocrinology, 50: 667672. Yang, K. and Challis, J.R.G., 199 I. Opioid receptors are present in the hypothalamus but not detectable in the anterior pituitary of the developing ovine fetus. Neuroendocrinology, 53: 623627. Yogev, L., Gottriecg, A., Timan, B., Homonnai, Z.T. and Paz, G.F., 1985. Changes in LH and prolactin levels in diabetic male rats and the role of the opiate system in the control of their secretion. Life Sci., 37: 993-999. Young, K.H., Buhi, W.C., Horseman, N., Davis, 1.. Kraeling, R., Linzer, D. and Bazer, F.W., 1990. Biological activities of glycosylated and nonglycosylated porcine prolactin. Mol. Cell. Endocrinol., 71: 155-162.