4 A
. Prunier, H. Quesnel Livestock Production Science 63 2000 1 –16
Growth of the follicles up to 2–3 mm does not effect of nutrition on the hypothalamic–pituitary axis
require gonadotrophin support Driancourt et al., may have consequences on folliculogenesis and
¨ 1995; Brussow et al., 1996 but such growth seems
ovulation. to be controlled mainly by local ovarian factors such
as growth factors. Among healthy 1- to 4-mm 3.1. Influence of nutrition on circulating levels of
follicles present at luteolysis or at weaning, 15–25 gonadotrophins
are recruited and selected to undergo preovulatory growth and to ovulate 4–7 days later whereas the
3.1.1. Influence of feed restriction others become atretic. In the female pig, there is no
The effects of feed restriction on circulating levels clear evidence showing that the signal for recruit-
of LH and or FSH have been evaluated in numerous ment and selection of these follicles is an increase in
experiments involving premature and cyclic gilts, as FSH as has been proposed for numerous other
well as lactating and weaned sows Table 2. In mammalian species. Guthrie and Bolt 1990 and
these studies, control females are fed either ad Hunter et al. 1992 have not associated any vari-
libitum Kirkwood et al., 1987; Mullan et al., 1991; ation in gonadotrophin secretion with preovulatory
Cosgrove et al., 1992; Booth et al., 1994; Zak et al., growth and have suggested that, in cyclic gilts, the
1997, 1998 or close to ad libitum Flowers et al., decline in progesterone at luteolysis is the signal for
1989; Baidoo et al., 1992a; Prunier et al., 1993a,b; recruitment and selection. However, ovulation can be
Peltoniemi et al., 1997; Quesnel et al., 1998a,b, or induced during the luteal phase by exogenous gona-
receive 125–150 of the energy requirements for dotrophins showing that preovulatory growth may
maintenance Armstrong and Britt, 1987; Prunier and occur despite high levels of progesterone Caldwell
Peintre, unpublished data. In most studies, restricted et al., 1969. An increase in LH pulsatility around
females receive 10–65 of the control feed intake luteolysis van de Wiel et al., 1981; Flowers et al.,
which is below, equal or above energy requirements 1991; Kemp et al., 1998 or immediately after
for maintenance Table 2. In young females pre- weaning for review, see Quesnel and Prunier,
pubertal, mature and early pregnant gilts, growth is 1995, without any clear variation in FSH, has been
retarded Flowers et al., 1989; Prunier et al., 1993a; observed in numerous studies. Moreover, experi-
Peltoniemi et al., 1997 and may even be suppressed ments with gonadotrophin deprivation have shown
Armstrong and Britt, 1987; Cosgrove et al., 1992; that FSH is necessary to support follicular growth
Booth et al., 1994, 1996 by feed restriction. During beyond 2–3 mm and LH beyond 4 mm Driancourt
lactation, the level of feeding of restricted sows is ¨
et al., 1995; Brussow et al., 1996. Therefore, it can never sufficient to meet energy requirements for
be concluded that recruitment and selection of the maintenance plus milk production and feed intake of
preovulatory follicles can occur only when the control sows is also below requirements in most
equilibrium between stimulatory factors at least LH studies Table 2.
and FSH and inhibitory factors e.g. progesterone in Detailed analyses of the data show that LH
cyclic females or hormones induced by suckling in pulsatility is inhibited during the period of feed
lactating sows is displaced in favour of the stimulat- restriction in a majority of experiments regardless of
ory factors. As selected follicles develop, oestradiol the physiological stage seven out of 11 experiments,
and inhibin secretion increases, inhibiting further LH Table 2. The influence of feed intake on mean LH
and FSH release see Section 2.1, which probably plasma concentrations is less clear and mean LH is
induces atresia of the smaller follicles of the cohort. significantly reduced during feed restriction in only a
minority of experiments four out of 14 experiments, Table 2. Such a difference is probably due to
3. Main effects of nutrition on the methodological reasons as plasma LH between
hypothalamic–pituitary axis pulses is very low and often close to the limit of
detection of assays. After cessation of feed restric- Since the ovarian function is under the control of
tion, the inhibitory effect of underfeeding on LH the gonadotrophin hormones, LH and FSH, any
pulsatility is rapidly attenuated as observed in
A . Prunier, H. Quesnel Livestock Production Science 63 2000 1 –16
5 Table 2
a
Influence of feed restriction on the number of LH pulses 6 h and on mean concentrations of LH and FSH ng ml
c b
Physiological stage Refs.
Feed supply LH pulses
Mean LH Mean FSH
High Low
High Low
High Low
High Low
Prepubertal gilts 1
330 100
– –
0.18 0.21
43.6 44.7
2 250
160 1.60
1.10 0.60
0.56 1.53
2.07 3
330 100
– –
0.19 0.17
28.4 30.0
4 330
100 –
– 0.40
0.28 –
– Mature gilts
After ovariectomy 5
125 15
4.60 1.60
2.60 1.50
133 144
Luteal phase 6
270 135
0.90 0.90
– –
2.4 2.2
Early mid luteal phase 6
270 135
1.80 1.10
– –
2.6 1.4
Early pregnant gilts Winter
7 230
115 1.40
0.60 0.90
0.90 –
– Summer
7 230
115 1.10
1.00 0.90
0.90 –
– Lactating females
First-litter sows 8a
100 60
1.60 1.85
0.30 0.38
34.1 43.5
8b 90
50 1.35
0.85 0.21
0.20 37.1
60.4 9
80 50
– –
– –
2.1 2.1
10 80
45 0.88
0.07 0.12
0.09 24.0
38.0 11
90 50
1.50 0.17
0.69 0.71
2.67 2.35
12 85
50 1.35
0.10 0.29
0.22 –
– Second-litter sows
13 85
45 –
– 1.90
1.30 –
– 14
80 45
– –
0.65 0.48
1.61 1.25
Weaned sows First-litter sows
8a 100
60 3.60
3.85 0.57
0.81 44.7
46.0 restricted during
8b 90
50 3.05
1.60 0.49
0.28 52.6
59.1 lactation
9 80
50 –
– –
– 2.4
2.4 11
90 50
0.83 0.50
0.86 0.87
2.57 2.77
12 85
50 3.25
1.90 0.45
0.36 –
– Multiparous sows
restricted after weaning 15
150 50
– –
0.95 0.87
2.64 2.25
a
Note that, in weaned sows, feed restriction occurred before gonadotrophin measurement in most studies in contrast to other physiological stages.
b
Feed supply is the estimated ratio between metabolic energy intake and requirements for maintenance MAINT in prepubertal, mature and pregnant gilts, and in sows restricted after weaning or for maintenance 1 milk production MAINT 1 MILK in lactating sows.
When this ratio was not indicated in the publication, it was necessary to calculate it. The following equations derived from Noblet et al.
0.60
1990,1999 were used: metabolic energy intake 5 0.95 3 digestible energy intake; MAINT MJ 5 1.0 3 liveweight kg for prepubertal
0.75
and mature gilts; MAINT MJ 5 0.44 3 liveweight kg for pregnant gilts and weaned sows; MAINT 1 MILK MJ 5 0.46 3 liveweight
0.75
kg 1
28.59 3 daily gain of the litter kg 2 0.52 for lactating sows.
c
List of references: 1 Cosgrove et al., 1992; 2 Prunier et al., 1993a; 3 Booth et al., 1994; 4 Booth et al., 1996; 5 Armstrong and Britt, 1987; 6 Flowers et al., 1989; 7 Peltoniemi et al., 1997; 8 Mullan et al., 1991 a: six piglets, b: 12 piglets; 9 Prunier et al.,
1993b 10 piglets; 10 Zak et al., 1997 six piglets; 11 Quesnel et al., 1998a 9–10 piglets; 12 Zak et al., 1998 8–10 piglets; 13 Kirkwood et al., 1987 11 piglets; 14 Baidoo et al., 1992a eight piglets; 15 Prunier and Peintre, unpublished data 8–10 piglets.
P , 0.05 between high and low groups, within hormonal criteria.
weaned sows Quesnel et al., 1998a and in prepub- antisera used in FSH radioimmunoassays differs
ertal gilts Booth et al., 1996. from one antiserum to the other. However, within a
Mean concentrations of plasma FSH differ greatly given experiment, a single antiserum is used, thus
between experiments ranging from less than 2 ng ml allowing the comparison between treatment groups.
to more than 50 ng ml Table 2. Numerous iso- Mean concentrations of plasma FSH are not clearly
forms of FSH are present in the blood and it is likely modified by feed restriction: no effect or a significant
that the number of isoforms recognized by the increase or decrease can be observed Table 2. The
6 A
. Prunier, H. Quesnel Livestock Production Science 63 2000 1 –16
increase in plasma FSH in restricted sows as shown by Mullan et al. 1991 may reflect a lower secretion
of inhibin due to the inhibition of folliculogenesis.
3.1.2. Respective influence of protein and energy The influence of protein restriction on LH secre-
tion in females receiving high amounts of energy and, reciprocally, the influence of energy deficit in
females receiving adequate amounts of proteins have been investigated in few studies. Some researchers
tried to analyse the influence of lysine which is the principal limiting amino acid in the pig Tokach et
al., 1992a; Jones and Stahly, 1995. However, they increased the intake of protein and of numerous other
amino acids together with that of lysine. Results
Fig. 2. Predicted influence of daily lysine and energy intakes
obtained in primiparous sows which were protein
27.2, 48.1 and 69.0 MJ of metabolic energy day on LH
restricted during lactation suggest that LH secretion
secretion in lactating sows adapted from Tokach et al., 1992a.
is inhibited during lactation and that this inhibition is
Increasing amounts of lysine are confounded with increasing intakes of proteins.
still present after weaning Table 3. Similarly, pulsatility and mean plasma concentrations of LH
can be reduced by energy restriction alone in lactat- production, the LH response to the lysine protein
ing sows Koketsu et al., 1996. intake is suppressed in lactating sows.
King and Williams 1984a as well as Tokach et al. 1992a investigated the influence of lysine pro-
3.2. Influence of nutrition on the pituitary stores of tein intake under various levels of energy intake in
gonadotrophins lactating primiparous sows. They showed that the
effects of lysine protein and energy intake are Feed restriction induces an increase in the pituitary
interdependent: LH secretion Fig. 2 and the per- content of LH in cyclic gilts Cooper et al., 1973. In
centage of sows with a short weaning-to-oestrus prepubertal intact gilts, as well as in ovariectomized
interval Fig. 3 increase with the lysine protein mature gilts, LH and FSH release after GnRH
intake only when energy is sufficient, and vice versa. administration is higher in animals having the lower
From these data, it can be calculated that, below 50 feed intake Armstrong and Britt, 1987; Cosgrove et
of the total energy requirements maintenance 1 milk al., 1992; Prunier et al., 1993a. These observations,
Table 3 Influence of protein lysine restriction during lactation on LH secretion of primiparous sows observed during lactation or after weaning
Reference Experimental group
Control Protein restricted
Number of pulses 6 h Lactation
King and Martin, 1989 7–8 piglets 0.68
0.43 Jones and Stahly, 1995
1.22 0.48
Post-weaning King and Martin, 1989 7–8 piglets
1.62 1.65
Mean plasma LH ng ml Lactation
King and Martin, 1989 7–8 piglets 0.54
0.38 Jones and Stahly, 1995
0.24 0.17
Post-weaning King and Martin, 1989 7–8 piglets
0.94 0.74
P , 0.05 between control and protein-restricted groups.
A . Prunier, H. Quesnel Livestock Production Science 63 2000 1 –16
7
Fig. 3. Influence of daily energy 25.1–69.0 MJ of metabolic energy and lysine protein intakes during lactation on the percentage of sows with a normal weaning-to-oestrus interval WOI. A Adapted from King and Williams 1984a; B adapted from Tokach et al. 1992a.
coupled with those concerning LH pulsatility, sug- any difference between experimental groups. In
gest that feed restriction inhibits LH release more addition, Barb et al. 1991 observed that the LH
than LH synthesis. This might result in an increase in response to GnRH was lower in prepubertal gilts
the pituitary stores of gonadotrophins in under- receiving an intravenous bolus of glucose than in
nourished females. Therefore, inhibition of the those injected with saline. Therefore, the effect of
GnRH pulse generator system could be one of the glucose on LH secretion is not clear. Moreover, it is
mechanisms explaining the effects of nutrition on confounded with that of insulin and other hormones
reproduction in the female pig. involved in the control of glucose homeostasis
growth hormone and cortisol for example since 3.3. Nutritional mediators
manipulation of plasma glucose has immediate con- sequences on release of these latter hormones.
Numerous hormones and metabolites are likely to Circulating levels of insulin can also be manipu-
mediate the effects of nutrition on the hypothalamic– lated by controlling the feed intake of carbohydrates,
pituitary axis. It can also be hypothesized that by inducing diabetes mellitus e.g. streptozocin-in-
nutritional-associated variations in hepatic portal duced diabetes or by the administration of insulin.
blood flow have consequences on the metabolic All of these possibilities have been used in the pig to
clearance of sex steroids and hence on the negative explore the effects of insulin on reproduction. Feed-
feedback exerted by the ovaries on the hypo- ing a starch-rich diet to multiparous sows stimulates
thalamic–pituitary axis. LH pulsatility at day 7 of lactation but not at days 14
or 21 and increases the preovulatory surge of LH 3.3.1. Glucose and insulin
occurring after weaning Kemp et al., 1995. In In order to determine the influence of glucose on
normal prepubertal or cyclic gilts, administration of LH secretion, various researchers have compared
insulin, using either the intravenous or the subcuta- plasma LH in animals infused with glucose or saline.
neous routes, provokes hypoglycemia whereas it has Results from these studies are conflicting and dif-
variable effects on LH release: it may stimulate or ficult to interpret. Booth 1990 observed a positive
have no effect Cox et al., 1987; Matamoros et al., effect of glucose on LH pulsatility in feed-restricted
1991. In diabetic mature gilts which were intact or gilts; this was in contrast to Tokach et al. 1992b
ovariectomized, LH secretion remains relatively high who, using underfed lactating sows, did not show
in the days following withdrawal of insulin therapy
8 A
. Prunier, H. Quesnel Livestock Production Science 63 2000 1 –16
Cox et al., 1994. Therefore, lack of insulin does contribution of high levels of FFA to the effects of
not seem to alter LH secretion during a relatively undernutrition on the hypothalamic–pituitary axis of
long interval of time 4–6 days. Such an hypothesis the female pig.
is in agreement with the results of Rojkittikhun et al. 1993a who showed that LH pulse frequency and
3.3.3. Adrenal hormones mean plasma concentration are not altered in lactat-
Plasma concentrations of corticosteroids may be ing primiparous sows which were fasted for 24 h,
increased under feed restriction in the pig Rafai and despite very low concentrations of insulin 2.5 vs. 29
Fodor, 1980; Baidoo et al., 1992a; Prunier et al., m
IU ml in fed sows and glucose 2.6 vs. 6.4 mmol 1993a. These hormones have inconsistent effects on
ml in fed sows. However, the lack of insulin may be basal LH secretion in the pig: they may have positive
detrimental for LH release if it is prolonged: LH Pearce et al., 1988, negative Fonda et al., 1984;
pituitary stores, as well as the in vitro response of Estienne et al., 1991 or no effects Fonda et al.,
pituitary cells to GnRH stimulation, are sharply 1983, 1984 in prepubertal and or ovariectomized
decreased in diabetic females where insulin therapy mature gilts. However, it seems relatively clear that
has been withdrawn for 7 days Angell et al., 1996. corticosteroids are able to decrease the LH response
Moreover, it has been demonstrated that diabetic to exogenous GnRH prepubertal gilts: Pearce et al.,
ovariectomized gilts are not able to respond to the 1988 and to block the preovulatory surge of LH and
positive feedback of oestradiol when insulin therapy subsequent ovulation cyclic gilts: Liptrap, 1973;
has been withdrawn for 7 days Angell et al., 1996. Barb et al., 1982. Therefore, activation of the
Therefore, it seems that insulin has positive effects adrenal axis during acute feed restriction may be
on LH secretion but it is unlikely that variations implicated in disturbance of ovarian activity of the
associated with nutrient absorption after each meal or female pig.
with differences in level of feeding have marked effects on LH secretion in the female pig unless
3.3.4. Other mediators these variations are extreme. Similarly, it does not
The role of neuropeptides in mediating the effects seem that variations in glycemia, within a physiolog-
of nutrition on LH secretion in the pig has received ical range, play a role in the effects of nutrition on
little attention until now. Endogenous opioids could reproduction.
be involved since it has been demonstrated that they inhibit LH pulsatility for review, see Kraeling and
3.3.2. Free fatty acids Barb, 1990. The only data concerning the influence
Plasma concentrations of free fatty acids FFA of endogenous opioids in underfed gilts have been
are elevated in fasting and in feed-restricted animals. published by Armstrong and Britt 1987 using a
Their influence on the hypothalamic–pituitary axis severe level of feed restriction, sufficient to induce
has rarely been investigated in the female pig. In cessation of oestrous cyclicity. These researchers
vitro studies have shown that oleic and linoleic acids compared LH release in control and underfed
increase basal LH release by pituitary cells whereas ovariectomized gilts before and after treatment with
they suppress the LH response to GnRH Barb et al., naloxone, an opioid antagonist. This drug failed to
1995. These results contrast with those obtained in restore LH mean concentrations and pulsatility in
vivo: a single intravenous infusion of a high dose of feed-restricted females. Therefore, arguments to sup-
FFA has a positive influence on the LH response to port the hypothesis that endogenous opioids are
GnRH and hourly infusion of the same dose of FFA implicated in the nutritional-induced inhibition of LH
induces an augmentation of the amplitude of LH pulsatility are still lacking in the pig.
pulses without any effect on their frequency in The involvement of leptin in mediating the effects
prepubertal gilts Barb et al., 1991; the major effect of nutrition on LH secretion is under evaluation in
of undernutrition on LH release is an inhibition of numerous species. Leptin is secreted by the adipose
the occurrence of pulses see Section 3.2. Therefore, tissue pigs: Ramsay et al., 1998, inhibits appetite
more studies are necessary to determine the exact pigs: Barb et al., 1998 and stimulates energy
A . Prunier, H. Quesnel Livestock Production Science 63 2000 1 –16
9
expenditure mice: Pelleymonter et al., 1995. Plas- ma levels of leptin seem to be lower in feed-re-
stricted than in control gilts Prunier and Quesnel, unpublished data. Therefore, leptin may be involved
in the effects of nutrition on reproduction, at least as a regulator of the nutritional status. Direct effects of
leptin at the hypothalamic–pituitary level could also play a role since RNA messengers coding for the
long-form leptin receptor have been detected in hypothalamic and anterior pituitary tissues of ewes
and since this expression in the ventromedial and arcuate nuclei of the hypothalamus is higher in
feed-restricted than in well-fed ewes Dyer et al., 1997. Moreover, leptin exhibits a high potency to
Fig. 4. Influence of daily feed intake high vs. low: 300 vs. 80
increase FSH and LH release from male rat
of the energy requirements for maintenance from luteolysis
hemipituitaries incubated in vitro, and to stimulate
induced by a prostaglandin analogue, alfaprostol on plasma
GnRH secretion from medio-basal hypothalamus
concentrations of progesterone in gilts adapted from Prunier et
explants Yu et al., 1997. Finally, leptin is able to
al., 1999.
stimulate LH secretion in vivo in mice and female rats subcutaneous injections: Ahima et al., 1996;
intracerebroventricular injections: Yu et al., 1997. metabolic clearance of oestradiol-17b may be de-
creased by feed restriction and influence LH secre- 3.3.5. Metabolic clearance of steroids
tion. However, growth and steroid secretion of the It has been demonstrated that hepatic portal blood
oestrogenic follicles are under the control of gona- flow and metabolic clearance rate of progesterone are
dotrophins see Section 2.2 whose release is in- decreased in ovariectomized gilts submitted to feed
hibited during feed restriction. Therefore, peripheral restriction Prime and Symonds, 1993. Moreover,
concentrations of oestradiol may not be increased lower concentrations of progesterone have been
and could even be decreased during feed restriction. observed in well-fed than in feed-restricted gilts at
Such a hypothesis is supported by the observation of the beginning of gestation Dyck et al., 1980; Dyck
lower concentrations of oestradiol-17b in restricted- and Kennedy, 1995; Jindal et al., 1996. Therefore,
fed than in full-fed gilts at 23 and 53 h after we have investigated in gilts whether plasma con-
induction of luteolysis by alfaprostol Prunier et al., centrations of progesterone around luteolysis could
1999. Similarly, concentrations of oestradiol-17b be modified by the level of feeding Prunier et al.,
were low in follicular fluid of oestrogen-active 1999. Regression of the corpora lutea was induced
follicles Spicer et al., 1991 and in plasma Rhodes at the end of the luteal phase by an injection of a
et al., 1996 of restricted-fed compared with well-fed prostaglandin-F a analogue alfaprostol. From the
heifers.
2
time of the alfaprostol injection, gilts received either 80 or 300 of the maintenance energy requirements
for 3 days. Progesterone was significantly higher in
4. Main effects of nutrition on the ovaries
