Abstract
Searching for the role of prolactin (PRL) in controlling gonadotropic axis activity
in sheep, we studied the effects of prolonged, intracerebroventricular (icv) PRL infusion
on luteinizing hormone (LH) secretion and catecholaminergic activity in the hypothalamic
infundibular nuclei/median eminence (IN/ME) in sexually active ewes during the periovulatory
period. Three groups of animals received the following treatments: 1) icv infusion
of PRL at a dose of 200 µg/day (Lower dose, n = 5); 2) icv infusion of PRL at a dose
of 400 µg/day (Higher dose, n = 6), and 3) icv infusion of the vehicle (control, n
= 5). Each dose of PRL was infused in a pulsatile manner, 4 × 50 µg/h and 4 × 100
µg/h, in 30-min intervals, respectively, during four consecutive days before oncoming
ovulation. The estrous behavior of ewes following treatments was also monitored as
a determinant of the GnRH/LH surge. Two series of blood collections were made in every
ewe, the first on the day preceding the infusion (day 0 of the experiment), the second
on the day after the infusion (day 5 of the experiment). In addition, on day 5 of
the experiment, perfusions of the IN/ME were made by the push-pull method, either
in control or lower dose-treated animals. It was shown that a significant (p < 0.01,
p < 0.001) increase in tonic LH secretion during the periovulatory period remained
in ewes irrespective of the kind of infusion. No statistical differences were found
in LH pulse frequency, amplitude, or in the length of the pulse when compared with
values from day 0 and 5 of the experiment within each group. A significant (p < 0.001)
increase in IN/ME perfusate concentrations of dopamine and noradrenaline metabolites
was noted in PRL-treated ewes in comparison with those in the control. The estrous
behavior in PRL-treated animals was delayed for a few days, 3.80 ± 0.80 days at the
lower dose (p < 0.01), and 2.83 ± 0.98 days at the higher dose (p < 0.05) in comparison
with the control, 0.20 ± 0.20 days. These data indicate that maintenance of an increased
PRL concentration within the central nervous system (CNS) for a few days before oncoming
ovulation has no inhibitory effect on tonic LH secretion. A few-day shift of the preovulatory
GnRH/LH surge, as determined by estrous behavior, might, however, be a consequence
of the PRL-induced increase in catecholamine turnover in the IN/ME.
Key words
Prolactin - LH - dopamine - noradrenaline - estrous behavior
References
1
Anderson S T, Walsh J P, Tillet Y, Clarke I J, Curlewis F D.
Dopaminergic input to the ventromedial hypothalamus facilitates the oestrogen-induced
luteinizing hormone surge in ewes.
Neuroendocrinology.
2001;
73
91-101
2
Arbogast L A, Voogt J L.
Prolactin (PRL) receptors are colocalized in dopaminergic neurons in fetal hypothalamic
cell cultures: Effect of PRL on tyrosine hydroxylase activity.
Endocrinology.
1997;
138
3016-3023
3
Ben-Jonathan N, Mershon J L, Allen D L, Steinmetz R W.
Extrapituitary prolactin: distribution, regulation, functions and clinical aspects.
Endocrine Rev.
1996;
17
639-669
4
Bertrand F, Thiery J-C, Picard S, Malpaux B.
Implication of D2-like dopaminergic receptors in the median eminence during the establishment
of long-day inhibition of LH secretion in the ewe.
J Endocrinol.
1999;
163
243-254
5
Cheung C Y.
Prolactin suppresses luteinizing hormone secretion and pituitary responsiveness to
luteinizing hormone-releasing hormone by a direct action at the anterior pituitary.
Endocrinology.
1983;
113
632-638
6
Chomicka L K.
Biogenic amines and the activity of the hypothalamo-pituitary-ovarian axis in ewes.
J Physiol Pharmacol.
1992;
43 (Suppl 1)
57-68
7
Chomicka L K, Wolińska-Witort E, Przekop F.
Release of LHRH, β-endorphin and dopamine by nucleus infundibularis/median eminence
during the estrous cycle in the ewe.
European J Endocrinol.
1994;
130 (Suppl 2)
43
8
Ciereszko R, Opalka M, Kaminska B, Kaminski T, Dusza L.
Prolactin involvement in the regulation of the hypothalamic-pituitary-ovarian axis
during the early luteal phase of the porcine estrous cycle.
Anim Reprod Sci.
2002;
69
99-115
9
Cramer O M, Parker C R, Porter J C.
Estrogen inhibition of dopamine release into hypophysial portal blood.
Endocrinology.
1979;
104
419-422
10
Curlewis J D, McNeilly A S.
Prolactin short-loop feedback and prolactin inhibition of luteinizing hormone secretion
during the breeding season and seasonal anoestrus in the ewe.
Neuroendocrinology.
1991;
54
279-285
11
Deaver D R, Dailey R A.
Effect of dopamine, norepinephrine and serotonin on plasma concentrations of luteinizing
hormone and prolactin in ovariectomized and anestrous ewes.
Biol Reprod.
1982;
27
624-632
12
Deaver D R, Dailey R A.
Effects of dopamine and serotonin on concentration of luteinizing hormone and estradiol
17-β in plasma of cycling ewes.
Biol Reprod.
1983;
28
870-877
13
Domański E, Chomicka L K, Ostrowska A, Gajewska A, Mateusiak K.
Release of luteinizing hormone-releasing hormone, β-endorphin and noradrenaline by
the nucleus infundibularis/median eminence during periovulatory period in the sheep.
Neuroendocrinology.
1991;
54
151-158
14
Fox S R, Hoefer M T, Bartke A, Smith M S.
Suppression of pulsatile LH secretion, pituitary GnRH receptor content and pituitary
responsiveness to GnRH by hyperprolactinemia in the male rat.
Neuroendocrinology.
1987;
46
350-359
15
Freeman M E, Kanyicska B, Lerant A, Nagy G.
Prolactin: structure, function and regulation of secretion.
Physiol Rev.
2000;
80
1523-1631
16
Gallegoz-Sanchez J, Malpaux B, Thiery J-C.
Control of pulsatile LH secretion during seasonal anoestrus in the ewe.
Reprod Nutr Dev.
1998;
38
3-15
17
Garcia A, Herbon L, Barkan A, Papavasiliou S, Marshall J C.
Hyperprolactinemia inhibits gonadotropin releasing-hormone (GnRH) stimulation of the
number of pituitary GnRH receptors.
Endocrinology.
1985;
117
954-959
18 Goodman R L.
Neuroendocrine control of the ovine estrous cycle. Knobil E, Neill JD The Physiology of Reproduction. 2nd ed., Vol. 2. New York; Raven
Press 1994: 659-710
19
Grattan D.
The actions of prolactin in the brain during pregnancy and lactation.
Prog Brain Res.
2001;
133
153-171
20
Kann G, Denamur R.
Possible role of prolactin during the estrous cycle and gestation in the ewe.
J Reprod Fertil.
1974;
39
473-483
21
Kochman H, Kochman K.
Purification of ovine and bovine prolactins on DEAE cellulose chromatography and preparative
polyacrylamide gel electrophoresis.
Bull Acad Sci Polon.
1977;
25
67-70
22
Kuljis R O, Advis J P.
Immunocytochemical and physiological evidence of a synapse between dopamine and luteinizing
hormone-releasing hormone-containing neurons in the ewe median eminence.
Endocrinology.
1989;
124
1579-1587
23
Merriam G R, Wachter K W.
Algorithms for the study of episodic hormone secretion.
Am J Physiol.
1982;
243
E310-E318
24
Misztal T, Romanowicz K, Barcikowski B.
Natural and melatonin-stimulated changes in the circadian rhythm of prolactin secretion
in the ewe during seasonal anestrus.
Neuroendocrinology.
1997;
66
360-367
25
Misztal T, Romanowicz K, Barcikowski B.
Effect of prolactin infused into the third brain ventricle on LH secretion in follicular-phase
and ovariectomized ewes.
Anim Reprod Sci.
2003;
75
27-37
26
Moenter S M, Caraty A, Lacatelli A, Karsch F J.
Pattern of gonadotropin-releasing hormone (GnRH) secretion leading up to ovulation
in the ewe: existence of a preovulatory GnRH surge.
Endocrinology.
1991;
129
1175-1182
27
Moore K E.
Interactions between prolactin and dopaminergic neurons.
Biol Reprod.
1987;
36
47-58
28
Picazo R A, Gonzalez de Bulnes A, Gomez Brunet A, del Campo A, Granados B, Tresguerres J,
Lopez Sebastian A.
Effects of bromocriptine administration during the follicular phase of the oestrous
cycle on prolactin and gonadotrophin secretion and follicular dynamics in Merino monovular
ewes.
J Reprod Fert.
2000;
120
177-186
29
Przekop F, Skubiszewski B, Wolińska E, Domański E.
The role of catecholamines in stimulating the release of pituitary ovulating hormone(s)
in sheep.
Acta Physiol Pol.
1975;
26
433-437
30
Reeves J T, Arimura S, Schally A B.
Serum levels of prolactin and luteinizing hormone in the ewe at various stages of
the estrous cycle.
Proc Soc Exp Biol Med.
1970;
134
938-942
31
Sortino M A, Wise P M.
Effect of hyperprolactinemia on luteinizing hormone and prolactin secretion assessed
using the reverse hemolytic plaque assay.
Biol Reprod.
1989;
41
618-625
32
Smith M S.
A comparison of pituitary responsiveness to luteinizing hormone-releasing hormone
during lactation and the estrous cycle of the rat.
Endocrinology.
1978;
102
114-120
33
Smith M S.
Effect of pulsatile gonadotrophin-releasing hormone on the release of luteinizing
hormone and follicle-stimulating hormone in vitro by anterior pituitaries from lactating and cycling rats.
Endocrinology.
1982;
110
882-891
34
Stupnicki R, Madej A.
Radioimmunoassay of LH in blood plasma of farm animals.
Endokrinologie.
1976;
68
6-13
35
Stupnicki R, Kula E.
Direct radioimmunoassay of progesterone in human plasma.
Endokrinologie.
1982;
80
1-7
36
Thiery J-C.
Monoamine content of the stalk-median eminence and hypothalamus in adult female sheep
as affected by daylength.
J Neuroendocrinol.
1991;
3
407-411
37
Thomas G B, Cummins J T, Smythe G A, Gleeson R M, Dow R C, Fink G, Clarke I J.
Concentrations of dopamine and noradrenaline in hypophysial portal blood in the sheep
and rat.
J Endocrinol.
1989 a;
121
141-147
38
Thomas G B, Cummins J T, Doughton B W, Griffin N, Smythe G A, Gleeson R M, Clarke I J.
Direct pituitary inhibition of prolactin secretion by dopamine and noradrenaline in
sheep.
J Endocrinol.
1989 b;
123
393-402
39
Tillet Y.
Distribution of neurotransmitters in the sheep brain.
J Reprod Fertil Suppl.
1995;
49
199-220
40
Tomaszewska-Zaremba D, Mateusiak K, Przekop F.
The involvement of GABAA receptors in the control of GnRH and β-endorphin release, and catecholaminergic activity
in the preoptic area in anestrous ewes.
Exp Clin Endocrinol Diabetes.
2002;
110
336-342
41
Tortonese D J, Brooks J, McNeilly A S.
Prolactin receptor gene expression in sheep hypothalamus and pituitary gland.
J Reprod Fertil Abstr Ser.
1995;
16
20
42
Tortonese D J, Brooks J, Ingleton P M, McNeilly A S.
Detection of prolactin receptor gene expression in the sheep pituitary gland and visualization
of the specific translation of the signal in gonadotrophs.
Endocrinology.
1998;
139
5215-5223
43
Traczyk W, Przekop F.
Methods of investigation of the function of the hypothalamus and hypophysis in chronic
experiments in sheep.
Acta Physiol Pol.
1963;
14
217-226
44
Wolińska E, Polkowska J, Domański E.
The hypothalamic centers involved in the control of production and release of prolactin
in sheep.
J Endocrinol.
1977;
73
21-29
Ph.D. Tomasz Misztal
The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences
05-110 Jabłonna n/Warsaw
Poland
Phone: + 48227824422
Fax: + 48 2 27 74 20 38
Email: t.misztal@ifzz.pan.pl