March 1, 2006

Female Reproductive Function: The Way of Life


By Dr. Howard Glicksman

The Basics
Human sexual reproduction involves the male being able to deposit his sperm deep into the female’s vagina to enable it to go meet the egg within her uterus. The last two columns dealt with some of the male aspects of this process in regard to what it takes on a biomolecular level to get a fertile male and what is required of his neurovascular system to effect a proper erection for adequate penetration. Now we move on to what must be happening in the female in order for reproduction and continuation of the species to take place. Here’s a link to the female reproductive system which you may need to review prior to continuing.

http://kidshealth.org/parent/medical/body_basics/female_reproductive_system.html

Once the male has deposited his sperm inside the female’s vagina her reproductive system takes over. From the bottom end the cervical mucus enhances the sperm’s ability to travel into the body of the uterus on their way to trying to meet up with the egg. At the top end the ovary, with several developing follicles (eggs), will eventually release a dominant one which is then gently coaxed into the uterus through the fallopian tube.

The sperm and the egg usually meet up in the tube where fertilization takes place. Then this new human person migrates along the tube back into the body of the uterus where he/she tries to implant in its lining (endometrium). If fertilization and implantation do not take place the lining of the uterus sheds and the woman experiences her monthly period.

The Menstrual Cycle (Ovarian Cycle) http://en.wikipedia.org/wiki/Menstrual_cycle
By convention the menstrual cycle begins with the first appearance of bleeding from the uterus through the vagina. This represents the shedding of the lining of the uterus. During the next two weeks the rising level of estrogen stimulates the lining of the uterus to grow; the so called proliferative phase of the endometrium. At the same time many follicles in the ovaries are developing on their way to one becoming dominant: the so called follicular phase of the ovary.

Eventually one egg erupts from the ovary and its remnants form what is called the corpus luteum (yellow body) which produces mainly progesterone. The progesterone tells the lining of the uterus to mature for the implantation of a fertilized ovum; the so called secretory phase of the endometrium. As for the ovary, with the development of the corpus luteum, it is said to be in the luteal phase.

But if fertilization does not take place the corpus luteum ceases to function after about 14 days and the levels of estrogen and progesterone drop. Since the growth and thickening of the uterine lining is dependent on these two hormones, once it is not being stimulated by them, it sheds from inside the uterus and a menstrual period begins again.

But what is the underlying mechanism that allows for this continuous monthly cycling

of ovulation and endometrial preparedness and shedding? It’s all in the hormones!!

Complexity of Survival Capacity
Before we go on to look at some of the specifics about hormonal control in the female reproductive system, I’d like to give you an overall picture of how these biomolecular systems work and what they accomplish toward our survival capacity.

The parameters for life; vital functions such as; blood pressure, temperature, respiratory and heart rate; blood chemical levels, such as; oxygen, carbon dioxide, sugar, sodium, potassium, and calcium; blood components, such as; red and white blood cells, platelets, and serum proteins; and hormones, such as; insulin, cortisol, thyroid and parathyroid hormone: and the pituitary and hypothalamic hormones; must stay within very narrow ranges for our survival.

We know that these parameters are monitored by specific sensors connected to specific cells, which then send specific messages to specific organs that receive the messages by way of specific receptors resulting in necessary changes in that parameter being made to allow for proper function and our continued survival. Medical science knows that if any one component of any one of these systems is absent or dysfunctional, the result is the loss of control of that parameter and usually death. This is one of the basic tenets of modern Medicine.

Blood pressure or temperature or respiratory or heart rate: too high or too low: DEATH
Blood sugar, or sodium, or potassium, or calcium level: too high or too low: DEATH
Red and white blood cells, or platelets or proteins: too high or too low: DEATH
Insulin, cortisol, or thyroid or parathyroid hormone levels: too high or too low: DEATH

I think you get the picture: it’s not very pretty.

The information to produce each of the three components of any one of these systems ie. the specific sensor, the capacity for the cell to send a specific message, and the ability for the target organ to receive that message by way of a specific receptor, is encoded in our DNA. Theorizing only on how our DNA obtained the ability to produce a given biomolecule, such as hemoglobin or insulin, does not take into account the need for the presence of the other components to make the system work, and the inherent ability for each system to control a particular parameter resulting in survival capacity, and therefore, in itself is not sufficient to explain the development of life.

For the mere existence of parts should not assume a system of function and the mere existence of a functioning system should not assume adequate capacity for survival. Please keep in mind below that without each component the whole system fails and humanity is lost: it’s called infertility.

The Hormones and Hormone Receptors (see link below)
Female reproductive function is directly dependent on the complex interaction between several hormones that are produced in three different areas of the body. This is known as the hypothalamus-pituitary-ovary axis.

The hypothalamus secretes gonadotropin releasing hormone (GnRH) in a pulsatile fashion. Usually this release of GnRH occurs about once every 90 minutes early in the menstrual cycle and then increases during the follicular phase to about once every 60 minutes at ovulation and then recedes during the luteal phase leading up to menstruation.

GnRH stimulates the pituitary gland to produce the two gonadotropins known as Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). As you will soon see, both hormones play their own respective roles throughout the ovarian cycle. FSH dominates during the follicular phase leading up to ovulation and LH dominates at ovulation and the luteal phase

These two hormones in turn stimulate the ovary to produce estrogen and progesterone which go on to stimulate the lining of the uterus (endometrium). During the follicular phase, when FSH and estrogen dominate, the endometrium is said to be in the proliferative phase. Then, after ovulation and into the luteal phase, when the effects of progesterone dominate, the endometrium is said to be in the secretory phase, preparing for implantation and support of the fertilized egg that is coming its way.

Keep in mind that in order for these hormones to have their effects, the cells in the ovary that produce estrogen and progesterone need FSH and LH receptors and the cells in the lining of the uterus that are preparing for implantation of the fertilized egg must be equipped with estrogen and progesterone receptors. The information to produce each of these eight separate components (the individual hormones and each of their specific receptors) are contained within the human genome. Neither the hormones nor their receptors are useful unless they all coexist.

One more important thing to remember is that the serum level of each of these hormones is being monitored by either the hypothalamus or the pituitary gland which ultimately affects their secretion;

e.g FSH has a negative feedback effect on GnRH secretion which means that when the FSH level rises GnRH secretion slows from the hypothalamus;

early in the follicular phase, when the estrogen level rises it feeds back on the pituitary gland causing a reduction in FSH and LH secretion;

during the luteal phase when the progesterone level rises it feeds back on the hypothalamus to diminish GnRH secretion and ultimately FSH/LH secretion as well

http://sprojects.mmi.mcgill.ca/menstrualcycle/endocrinology.html

The Stage is Set
At birth all women possess within their ovaries the total complement of eggs for a lifetime. These eggs are contained in sacs which are made up of support tissue and at this stage they are known as primordial follicles. Each month after puberty, about 15-20 of these primordial follicles begin to mature in a process that usually results in one dominant follicle erupting and allowing the egg to travel into the uterus on a mission of species survival. What causes these primordial follicles to begin maturation is presently poorly understood, however, medical science does know a lot about what happens once the process begins and carries on to ovulation. A combination of well placed and well controlled hormones, receptors, and enzymes, working together is absolutely necessary for this rhapsody of reproduction to take place.

The Follicular Phase of the Ovary
This phase begins at the start of menstruation. At this point in time the uterus has just shed its lining due to the drop in estrogen and progesterone levels because of the demise of the corpeus luteum from the last menstrual cycle. The drop in these hormones now allows the pituitary gland to secrete more FSH and to a lesser extent LH as well.

Each ovarian follicle consists of the actual egg surrounded by support tissue. Two of the important cells within the follicle are the theca cells and the granulosa cells which I will refer to as T-cells and G-cells. www.uoguelph.ca/zoology/devobio/210labs/ovary4.html

The LH, by way of LH receptors, tell the T- cells in the follicles to produce androgens; like testosterone. But the androgens migrate over to the G-cells, where by way of FSH locking onto their FSH receptors, the androgens are enzymatically converted into estrogen. Therefore the combined effects of LH and FSH make the T-cells and G-cells mature and grow.

So estrogen production and follicle maturation are well on their way early in the follicular phase due to the combined effects of LH and FSH acting on their respective receptors in the T and G cells of the ovarian follicles.

At this point, as mentioned above, as the estrogen level begins to rise it feeds back on the pituitary gland and FSH secretion starts to drop, and to a much lesser extent LH. as well. So we have 15-20 developing follicles that are producing estrogen like mad and now we find out that the FSH that is largely responsible for this explosion of reproductive activity is about to be squashed at the source. What to do? How will a dominant follicle make its presence known and erupt to allow the egg to go in search of the one sperm that will result in a unique and unrepeatable human being if the FSH level is dropping?

Remember the specific hormone receptors that are needed for any of these hormones to work? Well now they come into play in a big way. It turns out that estrogen does a lot more than just stimulate the lining of the uterus to proliferate. Not only does it induce the T-cells and the G-cells of the follicles to grow, but it also tells the G-cells to express more FSH and estrogen receptors which allows them to react more and more with the estrogen and the dropping level of FSH. This in turn allows these follicles to produce more and more estrogen and the cycle repeats itself.

In other words, the effects of estrogen on the follicles results in a positive feedback loop that results in more and more estrogen being produced which not only has a proliferative effect on the endometrium and by the way, also makes the cervical mucus more compatible with sperm motility and survival, but also starts to set the body up for ovulation.

Ovulation
How the dominant follicle is selected is poorly understood but it has been noted that it always contains a relatively high concentration of FSH receptors. Therefore, as less and less FSH is available to the competing follicles, the one that is the most sensitive to FSH stimulation by way of having expressed more FSH receptors on its cell membrane, will continue to mature and produce lots of estrogen while the others die off, giving way to the dominant one.

At this point we are left with one dominant follicle that is producing lots of estrogen because of its positive feedback loop and its self-induced high density of FSH and estrogen receptors, heading for ovulation. But what happens now?

We said before that when estrogen levels rise it has a negative impact on FSH production.

But now something incredible happens. It appears that a very high estrogen level in the face of a very low progesterone level results in a positive feedback on the pituitary gland. This causes a spike in LH, and to a lesser extent, FSH secretion, the so called LH surge.

Without this LH surge ovulation will not take place and death to humankind is the result.

It just so happens that the dominant follicle is well prepared for this circumstance because FSH, LH and estrogen all induce its G-cells to increase their LH receptor content and with this surge in LH secretion it is perfectly prepared to respond.

The Luteal Phase
After ovulation, the remnants of the follicle form what is called the corpus luteum. Now that the G-cells are loaded with LH receptors, this tells the majority of them to convert over from making estrogen to producing progesterone. The progesterone plays an important part in not only ovulation but preparation of the entire female reproductive system for implantation and nurturing of the new human being inside of the womb by thickening up the endometrium.

Marked elevation of progesterone, as occurs in the luteal phase, results in inhibition of GnRH secretion from the hypothalamus and FSH and LH by the pituitary gland. If fertilization and implantation do not take place, then over the next several days, the corpeus luteum loses its FSH and LH receptors, the ability for the pituitary gland to sustain it is lost and it eventually dies. With the subsequent drop in estrogen and progesterone levels the lining of the uterus cannot be maintained as well and it sheds causing the beginning of menses and the whole cycle begins again

WHAT!!! ME (macroevolution) WORRY??
Even a casual look at all of the interdependent factors that are necessary for female reproductive function and fertility shows that they are irreducibly complex in that without any one of them, the whole system fails. Without GnRH to stimulate the pituitary, the gonadotropins, FSH and LH would not be released. And without FSH and LH, ovulation would not take place and the ovarian hormones, estrogen and progesterone, would not be present to stimulate proliferation and maturation of the lining of the uterus. And let’s not forget the need for the four specific receptors for FSH, LH, estrogen, and progesterone, in order for each of these hormones to even have an effect.

One must also keep in mind that the mere presence of the hormones and their respective receptors does not fully explain how ovulation and implantation of the embryo takes place. Don’t forget that there is a constant feedback of these different hormones on the pituitary gland and the hypothalamus which ultimately affects GnRH, FSH and LH secretion. How do these glands actually monitor these hormones and how do they know what to do to allow for proper reproductive function?

One needs to consider the changing sensitivity of each secreting organ to a given concentration of hormone within a given density of hormone receptors. And of course, one needs to remember that in the follicular phase with low estrogen levels, FSH/LH is suppressed, but just prior to ovulation, as the estrogen level peaks it now miraculously does the exact opposite by causing a positive feedback resulting in the LH surge without which ovulation would not take place.

Certainly in order for macroevolution to even make any sense at all, evolutionary biologists must be able to explain how these components came together in progressively functioning systems over time to allow for adequate fertility within a living organism.

Such concepts as detection, sensitivity, response, regulation, and function; to most experienced people would point to a “mind at work” “an intellect that has a plan”.

Scientific fields such as Archaeology and Forensics that are dependent on human experience and judgment to make logical predictions and determinations about the likelihood of intelligent agency demonstrate practical examples of how detection of intelligent design can apply to scientific endeavors.

Evolutionary biologists would seem to have defined the possibility of intelligent design right out of their discipline by determining beforehand that this universal experience is not considered valid. So rather than having to explain the inconsistencies contained within the dogma of neoDarwinism with what we know to be the truth about how life works, they simply choose to ignore it and count it out of consideration a priori.

As many people have wondered: “Why is answering the question “Is this designed?”

Science if answered in the negative but religion if answered in the affirmative?”

Answer: “This is only true when considering the narrow and highly speculative enterprise of “origin science” due to a materialistic bias.

Additional Points to Ponder

A Look at Oxytocin: The Love Hormone
All of our sensory devices, including pleasure, provide a protective and social function to allow for individual and overall human survival. It’s been shown recently that the region for trust and bonding in the brain is positively affected, more often in women, by the hormone oxytocin which is released in response to massage, petting, and orgasm.

This indeed may at least partially give us a biomolecular basis for sexual exclusivity and monogamous relationships. Based on this information, one could wonder if people who promote infidelity and promiscuity have either a genetic or acquired defect in their oxytocin-bonding system that prevents them from properly developing monogamous relationships. Nevertheless, the body would appear to have a biomolecular mechanism for bonding between the sexes which has proven to be beneficial for the survival of the species through the development of the family in order to protect the most innocent and defenseless of humanity: the newborn. http://www.oxytocin.org/oxytoc/index.html

hCG to the Rescue
Q. Ever wondered how the mother’s body is able to sustain endometrial function to allow for proper nurturing of her child before the placenta takes over since the corpus luteum only has a 2 week lifespan without fertilization? What exactly happens at fertilization to allow the corpus luteum to continue to perform the secretion of progesterone?

A. It’s the fertilized egg itself that has the biochemical capacity to secrete a hormone called human Chorionic Gonadotropin (hCG) that is responsible for sustaining the corpus luteum. Structurally, hCG is very similar to LH and it is what continues to stimulate the corpeus luteum to allow for the ability of the mother to sustain this new life in her womb.

Think about it!!! The mother and father do not do it all on their own after all. To be sure the mother’s body sends out the egg to meet the sperm that was deposited by the father. But it is the new life within the womb that has to do his/her share by sending out hCG in order that he/she may implant in the endometrium and, without defect or premature artificial intervention, be nurtured lovingly to extra-uterine life nine months later.

The Pill: Sometimes Abortifacient?
Below are several links that explain the controversy surrounding this question.

I have been practicing medicine for over 25 years and I have seen countless times where a given medication comes on the market with a supposedly well understood mode of action and spectrum of side-effects, only to find out later that there’s a lot of other things that it does in the body; sometimes predictable and sometimes unpredictable; and more importantly; sometimes considered a good thing , and sometimes considered a bad thing.

The first three articles, to my mind, present compelling scientific arguments that have made me realize, even more than before, that many people who use oral contraceptives to prevent pregnancy do so not uncommonly by preventing a fertilized egg from implanting in the uterus ie acting as an abortifacient and not a contraceptive.

Just reconsider what I have presented here regarding the delicate interrelationship between all of these hormones and the effects on their target organs to culminate in ovulation, fertilization, implantation and further fetal nurturing to full gestation.

Throwing estrogen and progesterone at it in order to try to prevent ovulation made physiological sense at the time. But now with low estrogen doses, interaction with other medication, and not infrequently, poor patient compliance; the chances of breakthrough ovulation and subsequent fertilization becomes quite significant.

Of course, there are probably many people who use oral contraceptives who really don’t care how they work, as long as they don’t get pregnant. But I imagine that there are many people who would be horrified and angry to think that because of their pill use, they may have had, at one time or another, not artificial contraception but an artificially supported spontaneous abortion.

The authors of the final article try to refute what seems to me to be at least some suspicious evidence that points to the pill at least occasionally acting as an abortifacient. They claim that if breakthrough ovulation and fertilization takes place, the formation of hCG by the zygote results in very high levels of estrogen and progesterone which should more than correct for the thinned out uterine lining that every pill user knows about, as evidenced by her scanty periods. However this assumes a lot about how these hormones may affect what is now known to be newly emerging factors that affect fertility while at the same time relieving themselves of any responsibility to inform the users of these pills of this possible complication.

For you see, the manufacturers of the pill have indeed already expressed this definite possibility in their information packets Here’s what the Physicians’ Desk Reference says about the pill.

How does the pill work?

1. Suppression of gonadotropins (FSH and LH); to prevent ovulation

2. Alteration of cervical mucus; to make it more difficult for sperm entry

3. Alteration of the endometrium; to reduce the likelihood of implantation

How many pregnancies/yr occur on the pill?

With “perfect use”: 0.5% (this is the ideal--keep dreaming)

With “usual use:” 5% ( this is what’s happening out there)

You figure it out. Look it over for a while and think about it.

Obviously people are getting pregnant on the pill, which means that breakthrough ovulation occurs quite a lot with usual use. This means that a significant percentage of ovulated eggs are either being prevented from being fertilized by changes in the cervical mucus, or since continued pregnancy does happen, at least some of them are being prevented from implanting as the PDR itself claims.

Can anyone be sure that the hormones that had been taken to try to prevent ovulation and failed did not in some way also prevent implantation after fertilization took place? Despite the arguments presented by those who claim that the pill can only rarely be considered abortifacient, based on the information in the PDR, I think it behooves every pill prescribing physician to notify their patients that if they happen to have breakthrough ovulation and get pregnant on the pill, that it is possible that it may act as an abortifacient by preventing implantation.

Finally, consider this statement on the pill by Mr. Frank Susman while representing a pro-abortion client before the Supreme Court. “The most common forms of what we generally in common parlance call contraception, IUDs, and low-dose birth control pills, which are the safest of birth control pills available, act as abortifacients.

In other words judge, you can’t get rid of abortion , because the commonest form of “contraception” (the low dose birth control pill) acts by abortion so you’d have to get rid of them too. Need I say more?

www.pfli.org/faq_oc.html
www.polycarp.org/larimore_stanford.htm
http://ccli.org/nfp/contraception/mdexplains.php
www.prolifephysicians.org/abortifacient.htm

Next time I’ll be talking about glucose regulation “How Sweet it is?”

Dr.G.
drhglicksman@yahoo.com

Howard Glicksman M.D. graduated from the University of Toronto in 1978. He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida. He now practices palliative medicine for a Hospice organization in his community. He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being. Comments and questions about this column or any of the previous ones are welcome at drhglicksman@yahoo.com

Copyright 2006 Dr. Howard Glicksman. All rights reserved. International copyright secured.
File Date: 03.01.06

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