--PLACENTAL AND FETAL HORMONES
-EFFECTS OF PREGNANCY ON HORMONES PRODUCED BY THE MOTHER
--THE PITUITARY GLAND HORMONES
--THE THYOID HORMONES
Hormones are chemical substances or messengers produced by endocrine glands that are released into the blood to act on specific tissues in our body and control specific processes necessary for the normal function of the body. Some of the well known endocrine glands in our body include the pituitary gland in the brain, the thyroid and parathyroid glands in the neck and the adrenal glands on the kidney. As early as the 10th day of conception, even before a woman misses her next menses, an early pregnancy can be confirmed by the presence of a positive blood pregnancy test. This test confirms the presence of HCG, a hormone produced by the fetus as early as about 5 days after fertilization. This is way much earlier than the time an ultrasound scan can detect the presence of a fetus in the womb. Therefore, one of the earliest changes that occur in pregnancy are changes in the hormones released into the mother’s blood stream. As a matter of fact, pregnancy can be described as a firework of numerous hormones produced by the fetus, the placenta and the mother, all tasked with the mandate of transforming the mother’s body to support the fetus, right from conception till many months after delivery, many women are are however battered by the effect of these hormones, especially in the first three months of pregnancy; these changes are nonetheless very important for the normal outcome of all pregnancies.
THE FETO-PLACENTAL UNIT
This is a term used to describe the interaction between the fetus and its placenta that results in the production of numerous hormones that alter the mother’s body in other to sustain pregnancy and lactation. In the first few days of life, soon after fertilization, the outer part of the embryo turns into cells that later becomes the placenta. These cells which are known as the trophoblastic cells are responsible for the initial production of many of the hormones that are necessary for the normal outcome of pregnancy before developing into the placenta by the 12th week of pregnancy, hence the term feto-placental unit. The placenta thereafter serves as a giant source of many hormones, while the fetus also produces some hormones from its various glands located within its body that act either directly on the fetus, the placenta and the mother after crossing the placenta. All these are crucial for the survival of the fetus and the successful outcome of a pregnancy.
PLACENTA AND FETAL HORMONES
HUMAN CHORIONIC GONADOTROPIN (HCG): This is is a hormone secreted by the trophoblastic cells of a newly developed embryo few days after fertilization. Every month after ovulation, the corpus lutuem produces progesterone and oestrogen in preparation for pregnancy. In the absence of pregnancy, the corpus lutuem dies and the level of progesterone eventually falls resulting in the onset of menstruation and the beginning of another menstrual cycle. But following fertilization, the HCG produced by the trophoblastic cells ensure the continuous secretion of both progesterone and oestrogen by the corpus lutuem until a time when the trophoblastic cells develop fully into the placenta and take over the production of these two hormones. Since in the absence of progesterone, the pregnancy fails and menstruation occurs, and since HCG is necessary for the continuous production of progesterone by the corpus lutuem, HCG is therefore important for the immediate survival of all pregnancies.
In the early pregnancy, the level of the HCG doubles every 36 to 48 hours peaking at about 8 to 10 weeks and beginning to decline at about 12 weeks of pregnancy soon after the placenta cells takes over the production of progesterone and oestrogen from the corpus lutuem rendering the corpus lutuem jobless. The corpus lutuem in turn withers and regresses due to the declining levels of HCG. Morning sickness experienced during the early phase of pregnancy is believed to be directly related to the level of HCG in the blood since these feelings reduces once pregnancy reaches the second trimester and the HCG level begins to decline in most women. Hyperemesis gravidarum, a condition associated with excessive vomiting in pregnancy is also common in conditions where there is excessive amount of HCG e.g. twin pregnancy and hydatiform mole. Finally, HCG is known to stimulate an increased production of erythropoietin, the hormone responsible for the production of red blood cells in our body.
PROGESTERONE: Progetserone along with oestrogen are the two main pregnancy hormones. They are initially produced by the corpus lutuem but later by the placenta from about the 12th week of pregnancy. Their level increases gradually peaking in the third trimester and dropping immediately after delivery. As a matter of fact the amount of progesterone and oestrogen produced in pregnancy is more than the total amount of the two hormones produced throughout a woman’s lifetime outside pregnancy. Progesterone is believed to be the main hormone responsible for the maintenance of pregnancy. It ensures adequate nourishment of the fetus by inducing a change in the endometrial lining of the womb such that immediately after ovulation, the lining of the womb begins to store up glycogen and other nutrients necessary for the growth of the embryo. It also directly relaxes virtually all the smooth muscles and the ligaments of the body creating a spiral effect that affect the function of almost all the organs in the body. One of the obvious effect is dilatation of all the blood vessels, causing an increased in blood flow to the womb, thereby increasing the transport of food to the unborn baby and the transport of waste product from the fetus. This is also partly responsible for the warmth and flushing of the skin seen in pregnancy as more blood flows to the skin. Another effect of this relaxation is that it helps to keep the womb calm and provide the fetus a calm environment for it to grow by preventing unnecessary contractions that may lead to the expulsion of the fetus. No wonder it is often prescribed in the first trimester to support the pregnancy before the placenta becomes fully developed in women deemed at high risk of miscarriage. Acting in concert with oestroen and prolactin, progesterone prepares and enlarges the breast for lactation. Specifically, it promotes the multiplication and the growth of the milk ducts of the breast tissue.
OESTROGEN: Similar to progesterone, this hormone acts almost on all the organs in the body, producing multiple effects on the various systems of the body. One of the most important effect is it’s direct effect on the growth of the muscles of the womb, causing it to increase both in the length and numbers, such that as the fetus grows, so does the womb expands to accommodate the fetus. Its level rises steadily in pregnancy, peaking just before the onset of labor and dropping immediately after delivery. It is believed to act with other hormones to orchestrate the onset of labour and in concert with prolactin and progesterone to prepare the breast for lactation. Although, it increases the deposition of fat in the breast increasing its size and its mass overall, it prevents the secretion of milk in pregnancy. It is believed to be directly responsible for the glow of pregnancy and the adiposity of pregnancy i.e. the addition of fat gained during pregnancy. Its direct effect on the other organs will be discussed under changes in those organs in subsequent articles on normal changes in pregnancy.
Adrenocorticotrophic hormone (ACTH), human placental lactogen (hPL), Corticotrophin-releasing hormone (CRH) are some of the other hormones produced by the placenta. ACTH acts on the adrenal glands of the fetus stimulating it to produce cortisol. It is also believed to act on the mother’s adrenal gland to induce cortisol secretion. Corticotrophin-releasing hormone (CRH) also acts on the fetal adrenal gland to stimulate dihydroepiandrosterone (DHEA) and cortisol secretion. The dihydroepiandrosterone (DHEA) is in turn converted to oestrogen by the placenta. The production of cortisol by the fetal adrenal glands and the HPL by the placenta peaks at the 3rd trimester when they both ensure the provision and availability of enough glucose for the fetus by reducing the mother’s response to her own insulin, forcing the mother to use other sources of energy e.g. fat and protein, while leaving glucose almost exclusively for the baby to use. Cortisol also increases the level of appetite of pregnant women notably in the second and third trimester in a bid to increase the availability of food and substrates for the fetus. Unfortunately in women prone to diabetes mellitus and those that are already diabetic, by blunting and acting against the action of insulin on the mother’s body, the former are prone to developing diabetes mellitus in pregnancy while the latter are prone to developing an increased risk of complications of their diabetes mellitus in pregnancy. Therefore, it is important to identify such women and manage them appropriately before they develop irreversible or life threatening complications. Finally, human placental lactogen is also known to act against the secretion of the human growth hormone by the brain while cortisol is important for ensuring the maturity of the various organs of the fetus.
EFFECTS OF PREGNANCY ON HORMONES PRODUCED BY THE MOTHER
Numerous changes in many of the hormones normally produced by the mother do occur in pregnancy. A few of the important ones are:
THE PITUITARY HORMONES
The pituitary gland is the seat of production of some of the most important hormones produced in the human body, many of which are tasked with the control of secretion of many other hormones produced in other parts of the body. Hence it is often referred to as the master gland. In response to pregnancy, significant changes occur in the activity and the size of the pituitary gland.
The secretion of Follicle stimulating hormone (FSH) and Leutinizing hormone (LH) by the pituitary gland are totally suppressed by the high levels of HCG, progesterone and oestrogen produced in pregnancy. Because both FSH and LH are responsible for the initiation and control of the regular menstrual cycles seen in non pregnant women, their suppression is essential in the prevention of the growth of new ovarian follicles and the prevention of any other potential pregnancy in the phase of an already existing pregnancy.
Secondly, the pituitary gland in response to the high level of oesrogen, secretes high level of prolactin reaching about 15 times the non pregnant level; this massive increase in function results in about an 100% increase in the size and blood supply to the pituitary gland which is even more marked with each pregnancy but normally reverses to its pre-pregnancy stage gradually after delivery. Because of its large size and an increase in the amount of blood that flow into the pituitary gland during pregnancy, the gland is very sensitive to any change in blood flow, such that any acute massive blood loss that occur during delivery that is not quickly replaced may cut off the blood supply to the gland, resulting in partial or total death of the gland and a widespread hormonal deficiency referred to as Sheehan’s syndrome. As mentioned above, the prolactin is important in preparing the breast for lactation. However, milk secretion by the breast is normally suppressed by the high levels of oestrogen hormone present in the blood, until immediately after delivery when the oestrogen level drops following the removal of the placenta. Prolactin secretion stimulated by breast feeding right after delivery has also been shown to increase the mother’s sensitivity to insulin after delivery, increase metabolism of glucose and reduce the need for insulin injections by diabetic mother in the post-natal period.
Oxytocin is another hormone produced by the pituitary gland. Although its secretion begins sometimes early in pregnancy, the uterus is not sensitive to it until during labor when its secretion also incidentally peaks. The secretion of the growth hormone by the pituitary gland on the other hand is reduced due to the effect of HPL produced by the placenta.
THE THYROID HORMONES
The thyroid gland is a gland located in the front part of the neck that secretes the thyroid hormones, triiodothyronine (T3) and thyroxine (T4). These hormones affect almost all processes in the body and controls the level of activities of the various systems of our body. When they are produced in excessively high amount, their blood level becomes too high and the body over functions resulting in what we call hyperthyroidism. When they are produced in very low amount and their blood level becomes way lower than normal, the body under performs and becomes sluggish in what we refer to as hypothyroidism. Because they are produced in a bound form attached to the a protein called thyroglobulin, they are present in the blood in both a bound inactive form and a free active form. It is the free or active form that acts on the body cells and determines the level of activity of the body and not the bound form.
The production of the thyroid hormones is normally under the action of thyoid stimulting hormone (TSH), a hormone produced by the pituitary gland in the brain. The HCG bears a close resemblance to the TSH and thus exerts some effect on the thyroid endocrine system. The high HCG level in the first trimester induces an increased production of thyroglobulin along with the bound form of the thyroid hormones, reduces the production of TSH by the pituitary gland but has little or no effect on the free thyroid hormones except for a slight increase seen in the free T4 levels. In the second half of the pregnancy when the HCG level reduces significantly, the TSH normalizes and the free T4 falls. Although this may sound abstract to many people, women who are being managed for thyroid diseases in pregnancy should know that the interpretation of thyroid function test in pregnancy should be done bearing in mind the above changes in pregnancy. Hence only the free thyroid hormones in the first half of pregnancy and both the free thyroid hormones and the TSH in the second half of pregnancy are used for interpretation of the thyroid fucntion test and not the total thyroid hormones nor the bound form of the thyroid hormones for women with thyroid disease in pregnancy.
Finally, because there is an increased loss of iodide through the kidney during pregnancy and because iodine is essential for the synthesis of thyroid hormones, women living in areas with low iodine intake may develop hypothyroidism and a form of endemic goitre due to the lack of iodine necessary to produce an adequate amount of thyroid hormones in pregnancy. The neck swelling or goitre is due to excessive activity of the thyroid gland in a bid to compensate for the lack of adequate thyroid hormones created by the lack of iodine in the diet of such women. Merely adding iodine into the food content of such women e.g. iodinized salts, will prevent or treat the goitre.
Many other hormones such as cortisol, antinatriuretic hormones, aldosterone, deoxycortisone and angiotensin II increase significantly in pregnancy in some cases up to ten times of non pregnant states. While their effects are too complex to discuss here, one thing is certain the successful outcome of pregnancy depends on the unhinged interaction and balance between these numerous hormones.
Yet, despite all the above functions of these hormones, some of the adverse changes seen in pregnancy are as a direct effect of some of these hormones. Changes such as morning sickness, vomiting, nausea, change in taste and mood have been directly attributed to the high levels of HCG present in the first half of pregnancy, while a reduction in many of these effects have been attributed to the declining levels of HCG in the second half of pregnancy. Similarly, the high levels of cortisol, hPL and other anti insulin hormones may also increase the risk of a mother developing diabetes and its complications in pregnancy. Since without the hormonal changes in pregnancy the survival of the fetus is impossible, understanding and knowing the various hormonal changes that occur in pregnancy is important in order to reassure, anticipate and manage accordingly pregnant women, especially when things are not going as expected.