Female Reproduction Parturition and l Actation
Parturition and lactation
The factors that stimulate
parturition (birth) in humans are
complex, and reflect a synchronized set of endocrine-related events (Fig. 28a).
As estrogen levels rise during pregnancy, they stimulate an increase in uterine
oxytocin receptors. The fetus grows rapidly near to the time of birth; its hypothalamus–pituitary system matures and activates the adrenal system, resulting in
increased secretion of cortisol, and there is evidence that the fetus produces
the oxytocin necessary for the onset of labour.
Cortisol is known to be important in
the initiation of labour in some mammals, for example the sheep, but it is not
known if fetal cortisol plays a similarly pivotal role in human parturi- tion.
The distension of the uterus caused by fetal growth may also contribute to
increased oxytocin receptor synthesis. Oxytocin, through its receptors, may
also stimulate prostaglandin (Pg) synthesis, particularly of PgF2
and PgE2. The prostaglandins are a group of oxygenated,
unsaturated, long-chain fatty acids with profound effects on virtually all
tissues, and PgE2 and PgF2 appear to act through the cAMP
second messenger system to increase cytosolic Ca2+ and thus uterine
contractility.
These two have a therapeutic role in
the induction of labour. During parturition, there is a profound fall in
maternal plasma estrogen and progesterone concentrations, but it is not known
what causes the rapid and sudden changes in the secretion of the female sex
hormones during labour.
There is evidence that nitric acid
donors ripen the human uterine cervix and the enzyme nitric oxide synthase is
upregulated during spontaneous human cervical ripening. Inflammatory mediators
may play an important role as well. The onset of labour is associated with a
large influx of leukocytes, mainly T lymphocytes, neutrophils and macrophages,
into the myometrium.
Lactation and the suckling reflex Although maternal prolactin (PRL) plasma levels
rise well before birth, their role in pregnancy is unknown. During pregnancy
the breast enlarges, due to the combined effects of PRL, placental lactogen,
cortisol, growth hormone, estrogens and progesterone on the growth of the
mammary lobular–alveolar system, but lactogenesis is virtually absent. Estrogen
and progesterone actually inhibit milk production through a direct inhibitory
effect on PRL receptor synthesis.
After birth, however, the
concentrations of these two sex hormones are relatively low, and PRL is allowed
to play its key role in promoting lactogenesis. Lactogenesis and milk secretion
begin very soon after birth. Milk is produced in the cells which line the
alveoli, and is composed of lactose (produced from glucose), milk proteins, the
most important of which are casein and whey, lipids, divalent cations, and also
antibodies, through which the mother temporarily transfers certain forms of
immunity to the baby. In humans, certain drugs are also carried in breast milk
and this may be an important consideration for women on long-term medication
such as antiepileptics or those using, for example, drugs of addiction.
There is evidence that PRL stimulates
milk production through stimulation of the phospholipase A2 second messenger
system and increased prostaglandin synthesis, resulting in increased mRNA for
casein. Cortisol and insulin are essential for this action of PRL. PRL has also
been shown to activate the transport of K+ and Na+
through an action on the Na+/Ka+– ATPase pump, which in
mammary tissue is confined mainly to the basolateral membranes of the mammary
epithelial cells.
The suckling reflex. PRL secretion from the anterior pituitary
lactotroph cell is controlled by a reflex, the neuroendocrine suckling
reflex (Fig. 28b). The secretion of prolactin is normally under the
inhibitory control of dopamine (called prolactininhibitory factor, or
PIF) from the hypothalamus. The neurotransmitter gamma-aminobutyric acid (GABA)
may mediate the release of PIF (Fig. 28c). When a mother begins nursing, or
suckling the baby, the mechanical stimulation of the nipple sends afferent
impulses through the anterolateral columns of the spinal cord, some of which
converge, eventually, in the supraoptic (SON) and paraventricular (PVN)
nuclei in the hypothalamus. Oxytocin is released from neurosecretory terminals
in the posterior pituitary, and travels in the bloodstream to the mammary
gland, where it contracts the mammary myoepithelial cells, resulting in an
explosive discharge of milk. The same reflex somehow lessens or removes the
inhibitory influence of dopamine, resulting in PRL release from the anterior
pituitary. The control of prolactin release by the brain is complex and not
fully understood. A novel prolactin-releasing peptide has been described in the
hypothalamus, but its role as a specific PRL-releasing factor is not
established. Thyrotrophin-releasing hormone (TRH), vasoinhibitory peptide (VIP)
and angiotensin II act in the hypothalamus to stimulate PRL secretion from the
anterior pituitary. Milk production is maintained for as long as nursing is
continued. In some poorer societies, a mother may lactate for up to 3 years,
during which time she is relatively infertile. During nursing, gonadotrophin
secretion from the pituitary is inhibited, and sex hormone production remains
low. This results in a form of natural contraception. Non-lactating women will
return to normal cyclic activity within about 4–5 weeks after birth, whereas in
lactating women there will be no ovarian follicular development while plasma
PRL levels remain elevated. After weaning, or the cessation of suckling, the
secretion of estradiol and of LH increases, reflecting the resumption of normal
ovarian function.
Prolactin has many other actions in
both males and females, many of which are still poorly understood. It is
released in stress, sleep, during eating and exercise, and is involved in hair
growth. During the normal menstrual cycle it appears to maintain LH receptor
production, and also to maintain LH receptors during pregnancy.
