Twenty One

Question 1

What are primordial oogonia? Describe their lifecycle before birth and until puberty.

Answer 1

Primordial oogonia are the germ cells that eventually develop into oocytes. At about the

middle of our fetal life, ( if you happen to be XX with normal ovaries), there are about 7

million of these oogonia that developed due to mitotic activity. Unfortunately, most of

these have to go. Mitosis then stops, and there are no more new oocytes ever produced.

Eventually, there are only 2 million oocytes at birth and then only 400,000 at puberty. The

unlucky ones just degenerate into atretic follicles.

During fetal development, the oocytes that are remaining start the process of meiosis, and

basically just stop in prophase 1 until the time of ovulation. This is due to some kind of

maturation-inhibiting factor in the follicular fluid, putting the brakes on the meiosis. Refer

to the picture of the ovary. We will go through the stages of folliculogenesis.

Question 2

Describe primordial follicles. Primary follicles. Secondary follicles. Graafian follicles.

Answer 2

Primordial Follicles are resting or inactive oocytes. They consist of the oocyte surrounded by a single layer of flattened follicular (soon to be granulosa) cells, and a basement membrane around the follicular cells. Remember the oocyte is resting in prophase. If these cells don’t become atretic, they advance on to…

Primary Follicles, which have a larger oocyte, and this mucopolysaccharide coating secreted by the oocyte called the zona pellucida. There are also cytoplasmic processes extending from the granulosa cells to the egg to probably nourish it. The surrounding follicular cells start to proliferate and become more cuboidal. after stimulation with FSH (more on this later). A thecal layer forms outside of the basement membrane and the
granulosa cells proliferate even more.

Secondary Follicles are when you start to see a cavity (antrum) form in the middle of some of the follicular/granulosa cells. This follicular fluid contains steroids, growth factors cytokines.

Graafian Follicles (tertiary) develop from continued FSH stimulation. The antrum (cavity) is quite large and causes a bulging on the surface of the ovary. The oocyte is 
sitting on a platform of granulosa cells called the cumulus oophorus. The granulosa cells that were initially and still surounding the egg are called the corona radiata. Now there are two thecal layers, an internal and external layer with the internal layer surrounding the basement membrane. The basement membrane has no vessels penetrating it, so everything from the vascular thecal layers reaches the granulosa cells and the oocyte via diffusion.

Question 3

What is ovulation? What triggers it? Describe the process.

Answer 3

Ovulation is the release of the oocyte from the ovary, triggered by the LH surge. This LH surge completes the first meiotic division right before ovulation. The result is an oocyte and the first polar body. This polar body is in the perivitelline space, which is the space within the zona pelucida. The second meiotic division occurs at the time of fertilization where there is a second polar body given off from the oocyte. Ovulation is a complex process. It is not due to increasing pressure in the follicle, causing an explosion of the egg into the pelvis. What happens is that the follicular wall is thinned out by collagenases and
plasmin which are proteolytic enzymes dissolving the follicular wall. The oocyte is extruded with the corona radiata, cumulus oophorus cells, and the follicular fluid.

Question 4

What is the corpus luteum? What is its function? What does it become?

Answer 4

Corpus Luteum is what remains of the follicle (literally “yellow body”). Both the theca

layer and the granulosa cells become lutineized, the latter producing progesterone. If

pregnancy results, then the corpus luteum supports the pregnancy until 8-10 weeks. If no

pregnancy results, the corpus luteum becomes scarred and fibrosed and is then called a

Corpus Albicans.

Question 5

What are the 3 types of estrogen? What is its origin?

Answer 5

Estradiol is the star here (“di”meaning two hydroxyl groups). It is the most potent and

most abundant estrogen around. It is mostly from granulosa cells as we will soon learn.

Estriol (three hydroxyl groups…hence the tri) is usually seen in pregnancy. Estrone (one

hydroxyl group) is the weakest. It is usually made in peripheral tissue from

androstenedione, seen in menopausal patients, and possibly obese patients.

Question 6

What are the progestins? What is their origin? What do they become? What is the significance of 17 alpha hydroxyprogesterone?

Answer 6

Progestins

Look at the steroid pathway figure. You can see how progesterone (the major progestin) is

not only a major steroid itself, but it is also a precurser to the estrogens and androgens.

Another big test topic is 17 alpha hydroxyprogesterone. This is the steroid that builds up

in congential adrenal hyperplasia caused by 21 hydroxylase deficiency.

Question 7

What are androgens? Examples? Are they secreted from the ovary? What are some other hormones involved in the ovary?

Answer 7

Androgens

Testosterone is secreted by the ovary, but not in large quantiaties. Androstenedione and

Dehydroepiandrosterone (DHEA) are also secreted, but mostly act as precursors. There are

several other factors in the ovary that are involved with autocrine and paracrine-like

activities. Some examples are insulin-like growth factors, cytokines etc.

Question 8

Describe the two cell theory of estrogen synthesis? Which hormones are important? When are they active? What reactions occur in which cells? What is the role of inhibin? How is feedback regulated? What enzymes are important?

Answer 8

Estrogen, for being such an important hormone, has a very round-about way of how it is

synthesized. The two cell theory explains this. The two cells being the granulosa cells and

the theca interna cells…both surround the oocyte and can be seen in the figure of the ovary.

(The theca interna cells are on the other side of the basement membrane, shown as squiggly

lines that are unmarked). The theca interna cells are analogous to the Leydig cells in the

testis, they both have LH receptors and they both are the predominant sites for androgen

production in the gonads, stimulated by LH. Granulosa cells are analogous to the Sertoli

cells in the testis. Both surround the germ cells, and respond to FSH. Granulosa cells also

make a hormone called inhibin, which inhibits the production of FSH.

For some reason, granulosa cells were not endowed

with the enzyme 17-hydroxylase and can not make

androgens, which are the precursors for estrogen.

(follow this through on the steroid pathway “chicken

wire” diagram). What happens is that the

androstenedione produced in the theca interna cells is

used as a precursor in the granulosa cells, and is

aromatized to estrogen by the enzyme called

armoatase. FSH and a small amount of LH secreted

during the first half of the menstrual cycle stimulate

the production of estrogen. This increasing estrogen

synergizes with FSH to help make some LH receptors

on the granulosa cells too…this will be important

later in the menstrual cycle.

FSH and LH both work on the cells using cyclic

AMP as a second messenger. Estradiol can inhibit

LH and FSH at both the hypothalamus and pituitary.

Inhibin is also a suppressor for FSH, working at the

hypothalamic/pituitary level.

Question 9

Describe the cellular mechanism of estrogen and progesterone.

Answer 9

Both the estrogens and progestins enter the cell by diffusion and bind to nuclear receptors.

After binding to the receptors, two of the receptor/hormone pairs join (dimerize) and then,

the dimerized pair join to the hormone response element (HRE) on the DNA. mRNA is

then produced and you know the rest of the protein synthesis story. Apparantly, there is a

heat shock protein (HSP) bound to the receptors before the steroids bind to them. After the

steroid binds to the receptor, the receptor dumps the HSP and changes its configuration

and marches with the newly bound steroid to the nucleus to go make protein.

Question 10

What are the main actions of the estrogens?

Answer 10

The main actions of the estrogens are as follows:

 Growth stimulation of the uterus, fallopian tubes, vagina, and endometrium (too much can lead to endometrial cancer) and mammary gland ducts.

 Moisturizes the vagina and causes the cervix to secrete thin, watery mucus

 Helps with follicular growth and with the formation of LH receptors on the granulosa cells

 Prevents osteoporosis at menopause

 Stimulates bone growth and closes the epiphyses (if too soon, patient will have shorter overall height)

 Decreases total cholesterol, LDL cholesterol, but increases HDL

 Increases clotting factors

 Decreases glucose tolerance

 Increases sex hormone binding globulin, thyroxine binding globulin, and transcortin

 Increases the number of progesterone receptors

Question 11

What are the main actions of progestins?

Answer 11

 Produces secretory endometrium for implantation of blastocyst.

 Turns cervical mucus viscous and scant

 Stimulates the alveolar and lobular development of the breasts

 Antagonizes aldosterone, therefore decrease sodium retention

 Increase body temperature

 Increases ventilation

 Decreases bowel and uterine motility

Question 12

What are the main actions of the androgens?

Answer 12

 Increase in pubic and axillary hair in women

 Excesses can cause increased midline hair (mustache, beard, male escutcheon etc.) also referred to as hirsutism

 Increased bone formation

 Precursors for estrogens

 Increase in libido

Question 13

What are the 3 faces of the ovarian cycle? How long do they last?

Answer 13

There are 3 phases to this. I will use the typical 28 day cycle (that really isn’t so typical clinically) to explain

1. follicular phase (lasts about 14 days but is variable. This is what may cause variation in cycle length)
2. ovulation
3. luteal phase (lasts about 14 days…is NOT as variable as the follicular phase)

Question 14

Describe the follicular phase of the ovarian cycle including the hormones involved, what they do, where they act, what cells are involved, etc.

Answer 14

Clinically speaking, the follicular phase begins with the menstrual cycle. I realize that it

seems more intuitive to end with the menstrual cycle, but from now on, you will refer to the

first day of menses as day #1. Basic scientists often refer to ovulation (or the LH peak), as

starting points, so don’t be confused.

To confuse you even more, the follicular phase actually starts in the prior luteal phase

phase when a crop of oocytes are getting all excited about being the DOMINANT

FOLLICLE! About 3 to 12 of these oocytes are selected (by FSH stimulation) to be the

dominant follicle, but like in the TV show, only one (generally speaking) gets to be the sole

survivor. FSH stimulates the growth of these select few, and via the two-cell hypothesis,

they start to secrete estrogen. These follicles secrete estrogen and by doing so, start

inhibiting FSH production, essentially starving themselves for that which is making them

grow. The dominant follicle, however, wins because it has more FSH receptors (by
chance) than any of the others. By having the most receptors, it needs less FSH than the

others and survives while the others become atretic and are lost forever.

Later in the follicular phase, we see progesterone just getting started. This is due to the

stimulation of the granulosa cells with LH. (FSH induces LH receptors on the granulosa

cells). Estrogen levels start reaching their peak just before ovulation, and in fact get the

ovulatory process going. Read on.

Question 15

What causes ovulation? When?

Answer 15

About 14 to 24 hours after the peak in estradiol, there is a surge of LH, which causes ovulation. This occurs about 10-12 hours after the peak in LH. This is ingenious because the follicle is actually telling the brain that it is ready for ovulation, thus getting the timing down perfectly.

Question 16

Describe the luteal phase. What cells are involved and what are they producing? What happens if pregnancy occurs? What happens if it does not occur? What regulates this?

Answer 16

This is the second half of the cycle, typically around 14 days in length, and the least

variable of the two halves. After the LH surge, the theca and granulosa cells become

luteinized, and the structure is then called the corpus luteum. The big product here is

progesterone, and a good amount of estradiol is produced too. The corpus luteum’s

survival is dependent on whether or

not pregnancy results. The hormone

HCG (human chorionic gonadotropin)

is what maintains the corpus luteum.

If pregnancy occurs, the HCG rescues

the corpus luteum from its demise, if

no pregnancy, the corpus luteum’s

progesterone production peaks at 7

days after ovulation, and then

decreases. The pregnancy itself, via

HCG, maintains the corpus luteum

and progesterone production to

ultimately maintain itself. Think of

progesterone as “pro gestation”.

If there is no pregnancy (and no

HCG), then the corpus luteum shrinks,

progesterone declines, and FSH levels

start to rise again, hence recruiting a

new crop of contestants for next

cycle’s dominant follicle. Remember

when we read about the cycle actually

starting in the prior luteal phase?

Well, hopefully it makes sense now.

Question 17

Describe the neuroendocrine control of LH/FSH secretion. What are the pulses like?

Answer 17

Our existence here on this planet has a lot to do with an important hormone called GnRH or

gonadotropin releasing hormone. Located in the arcuate nucleus in the hypothalamus, a

group of cells (which actually migrated from the olfactory region of the nose along the

olfactory nerve) is what controls this process. These cells secrete pulses of GnRH, which

ultimately drive the FSH and LH levels. They are influenced by many factors such as

ovarian steroids and opiates, to name a few. It is the pulsatile secretion of GnRH which

causes LH and FSH to be secreted in a pulsatile fashion as well. Generally, the pulses are

END 21-9

more frequent but smaller in the follicular phase compared to the luteal phase, with a slight

increase in frequency observed, as you get closer to ovulation.

Question 18

Describe the action of estradiol on the hypothalamus and pituitary.

Answer 18

Well, both actually. In the follicular phase, the slowly rising estradiol levels prime the

hypothalamus and pituitary so that LH levels rise slightly, rather than decline by negative

feedback. This is to get the pituitary geared up for the big LH surge. As the levels of

estradiol rise, and we see the presence of progesterone, we have everything ready for the

LH surge. When there is at least 200 pg/ml of estradiol, and progesterone present, there is

a positive feedback on the hypothalamus and pituitary causing the LH surge. The peak in

follicular estrogen is the trigger for the LH surge..the ovary’s way of telling the brain it is

ready for the LH surge. The presence of progesterone augments the LH surge.

In the luteal phase, the increased production of progesterone, estradiol and inhibin from

the corpus luteum cause a negative feedback on GnRH, LH and FSH.

There are SEVERAL other factors involved with this process, a great deal at the ovarian

level. There are several autocrine and paracrine factors, feedback loops etc. that all help

produce a single dominant follicle in women. You know the most important details.

Question 19

What are the 3 phases of the uterine/endometrial cycle? Describe the blood supply of the endometrium.

Answer 19

3 phases to know:

1) Menstrual phase-which starts off the cycle
2) Proliferative phase
3) Secretory Phase

Note the blood supply to the

endometrium (the innermost

lining of the uterus). This is

the part that is shed with

menstruation. It is supplied

by a basal artery, which

supplies the inner third of the

endometrium which does not

get shed, and the spiral

artery, which is coiled and supplies the outer 2/3 layer which does get shed.

It is somewhat hard to conceptualize what exactly the differences are between the secretory

and proliferative phases (also referred to the follicular and luteal phases), but I will try to make it clear.

Question 20

Describe the proliferative or follicular stage of the uterus.

Answer 20

What the uterine lining (endometrium) looks like in the first half of the cycle. Estrogen

stimulates its growth. Estrogen stimulates growth from the basal layer and causes the stroma to

“reinflate” itself. The glands are usually straight, opening into the uterine cavity. There is

increased mitotic activity seen as well. One also sees an increase in ciliated and microvillous

cells.

Question 21

Describe the secretory or luteal phase of the uterus.

Answer 21

After ovulation, the progesterone “transforms” the proliferatvive phase endometrium into one

that will allow implantation. We start to see the glands filling with secretions (hence the name

“secretory”). There is more glycogen storage in the cells and the spiral arteries become very

tortuous. Note that the endometrial height does not change during this phase. It maxed out at

the time of ovulation. What is different is that the glands and vessles do keep growing, and so

everything gets tortuous and crowded. This peaks at about one week after ovulation, which is

when the embryo decides to implant right into the endometrium. The HCG from the embryo

causes the ovary to make progesterone, to keep this nice endometrial lining just like it is. If

there is no embryo and no HCG, the progesterone level starts dropping. There is constriction

of the spiral arteries, prostaglandin release and necrosis. Basically it all just falls apart and all

the left-over outer 2/3 layer is sloughed off and we are back to a new menstrual phase and a

new cycle. The functional layer (that had the basal artery blood supply) was never shed and

thus begins a new proliferative phase to start the cycle over again.

Question 22

Describe the change in cervical mucus during the menstrual cycle.

Answer 22

We also see changes in the cervical mucus as well. Estrogen stimulates the production of

copious, watery, thin mucous that resembles egg white. This thin mucus is quite stretchy ,a

characteristic we refer to as “spinnbarkeit”~pronounced spin-bar-kite. A cool word to throw

out at your next social function. This stringy clear mucous helps the sperm get through the

cervical os in its destination to find the lucky egg. This estrogenized mucus also forms a “fern-
pattern” when placed on a slide and allowed to dry. This peaks at the time of ovulation, which

makes sense since it facilitates sperm. The rest of the cycle, the mucus becomes thick and

tacky and blocks the entry into the cervix.

Question 23

Describe the effect of the sex steroids on vaginal cells.

Answer 23

The sex steroids also influence the vaginal cells. Estrogen keratinizes or cornifies vaginal

cells. They are large, flat and irregularly shaped, with small nuclei. There are few leukocytes.

Progesterone stimulates smaller cells, few cornified cells and more leukocytes.

Question 24

Describe the rises and falls of FSH and LH that occur from prenatal life to puberty.

Answer 24

1) There is a peak in fetal FSH and LH concentrations in the second trimester of

pregnancy, these levels fall in the third trimester, probably due to negative feedback of

the sex steroids

2) There is a rise in LH and FSH shortly after birth. This is most likely due to the loss of

the maternal sex steroids that the fetus saw during the third trimester. Since there are

no more sex steroids to suppress the gonadotropins, they rise. This also implies that the

hypothalamus-pituitary-ovarian axis is functioning, even in the newborn.

3) FSH and LH remain at low levels until about 6-8 years of age. During this time, the

“gonadostat” is highly sensitive to negative feedback, HIGHLY, meaning very low

levels of estradiol suppress FSH and LH. The gonadostat is a term used to describe

some “setpoint” mechanism that exists in the brain. It is not an actual structure, but

used to describe whatever it is that makes the hypothalamus sensitive to negative

feedback. This will hopefully become clearer as you read on.
4) Whatever supresses the gonadostat is lost prior to puberty. We see increased GnRH

pulses with subsequent increases in LH and FSH secretion as well. LH is the big player

during this stage of life. With the increasing LH and FSH, we start to see the sex

steroids being produced from the ovary and thus the development of the secondary

sexual characteristics.

Question 25

What is thelarche? Adrenarche? Menarche?

Answer 25

Definitions to know:

1) Thelarche—breast development

2) Adrenarche—increase in adrenal androgens. This is the growth of the pubic and axillary hair. Note that this is separate from what was mentioned above. This has
its own schedule and it is somewhat coincidental that it all happens at the same time as the other pubertal events.

3) Menarche—the first menses

Question 26

What order do the pubertal events occur in?

Answer 26

Breast bud, pubic hair, growth, menarche, adult pubic hair, adult breast

Question 27

How does body fat affect pubertal timing and results.

Answer 27

There are several factors determining the timing of puberty, but one of the big ones is body fat.

Modestly obese girls have an earlier onset whereas intense exercisers have a delayed puberty.

These individuals have so little body fat that perhaps there is no fat to aromatize the androgens

into estrogens and they have amenorrhea, a fancy word for having no periods. Ballet dancers

are notorious for this. The problem is no estrogen and all the problems associated with it.

These individuals are a set up for osteoporosis (weakening of bone).

Question 28

Describe perimenopause. Describe how menopause occurs?

Answer 28

Menopause is essentially the cessation of menses. The mean age of menopause is about 51

years old. There is a time period in a woman’s life called the perimenopause, which is

when the cycles are becoming more and more irregular, and cycle lengths typically shorten

(that is the length of time between cycles, not the length of the menses). The point is that it

usually just does not abruptly happen, but there is some warning that “the change” is

coming.

What essentially happens is that the woman runs out of eggs (oocytes). Basically if you

nave no eggs, you have no granulosa cells and therefore, no estrogen. There are variants of

menopause called premature menopause where it may not be that simple. What may be

going on here is an FSH receptor problem on the granulosa cells. There may be eggs, but

for whatever reason, i.e. autoimmune, they don’t respond to the FSH. Women can also

prematurely run out of eggs too. More about that when you are on your OB/GYN rotation.

Aside from the negative feedback of estrogen, inhibin plays a big role here. The granulosa

cell makes inhibin, and when you run out of eggs/granulosa cells, you run out of inhibin.

Inhibin is what inhibits FSH. That is why you see the rise in FSH in menopausal women.

There is no more negative feedback and the FSH is “screaming” looking for an oocyte to

stimulate. That is a major clinical point because we measure FSH levels to determine if a

woman is menopausal.

Estrogen levels plummet. The vaginal mucosa atrophies. Bone loss starts immediately.

Cardiovascular disease increases and rises to the level seen in men. Women experience hot

flashes. Hormone replacement therapy is used to alleviate these symptoms. We will

discuss these hormones in detail later.

There are still some estrogens produced, mainly estrone. Due to the high FSH/LH levels

produced from the pituitary, androgen production may still continue (hence the increased

facial hair sometimes seen in postmenopausal women). These androgens are aromatized in

fat to estrone. In some individuals, especially obese, this estrone can still stimulate the

endometrium, and eventually lead to endometrial cancer. Postmenopausal uterine bleeding

is ALWAYS considered to be uterine cancer until proven otherwise!

Question 29

What is PMDD? What are the symptoms? Treatment?

Answer 29

This is now referred as PMDD…premenstrual dysphoric disorder. I guess PMS is

politically incorrect. This is a syndrome that needs to be documented with a menstrual

calendar for several months before it can be called this. What you have to see is symptoms

in the LUTEAL phase that end with menstruation. Otherwise you can’t call it PMS or

PMDD. Symptoms can include irritability, depression, bloating, weight gain, breast

soreness etc. There have been SEVERAL proposed ways to treat this. The only clinically

proven way to treat this effectively is with medications such as Prozac (fluoxetine). Prozac

works so well on these symptoms, that they are now marketing the same drug…but they

just changed the name to Sarafem. I guess Prozac may have a bad connotation. Pretty

sneaky huh?

Question 30

Describe dysmenorrhea. Treatments?

Answer 30

Painful periods. The pain is probably prostaglandin mediated so NSAIDs are a good

choice for these patients. We can also use oral contraceptives, which decrease the amount

of bleeding and prostaglandins. There are other anatomical causes (endometriosis, fibroids) which you will learn about next year.

Question 31

Describe Turner’s syndrome. Treatment?

Answer 31

45 XO karyotype. You need both X chromosomes to develop normal ovaries. With just

one, they turn into a streak of fibrous tissue, devoid of oocytes. What you see is primary

amenorrhea. Typical features include webbed neck, shield chest, short fourth metacarpals.

These women have sexual infantalism because they have no estrogen production. They do

have a uterus! These girls will menstruate with hormonal therapy. They can be given oral

contraceptives or hormonal replacement therapy.

Question 32

Describe some features of PCOS. Pathogenesis?

Answer 32

Chronic anovulation with hyperandrogenism, or put more simply, hairy women with irregular menses. There is a big spectrum with this. Not all women are hairy, but there are
elevated androgens. The LH levels are higher than FSH, typically in a 3:1 ratio (on boards). In a prior illustration, the you can see that the LH and FSH levels fluctuate during
the menses, but not in these women. They are stuck with elevated LH’s and relatively low FSH levels. The high levels of LH stimulate the theca cells, hence increased androgens.

There is still some estrogen production (a lot due to the aromatization of the androgens) which constantly stimulate the uterus. Since these people don’t ovulate, they don’t make progesterone. Chronic estrogen without progesterone can lead to uterine cancer eventually. This is after several years of being untreated.

Another aspect of PCOS is hyperinsulinemia. These patients are a set-up for diabetes in the future. The increased insulin can lead to cardiovascular disease. The insulin (via insulin like growth factor receptors) also contributes to the increased androgen production.

Basically it is an endocrinologic mess. We treat this with either oral contraceptives or insulin lowering agents. If they are trying to get pregnant, we can start with clomiphene citrate. More detail next year.

Question 33

Describe the stimulation of the female endocrine act.

Answer 33

This depends on both psychic stimulation and local sexual stimulation. Sexual thoughts

can lead to desire, which may enhance the performance of the sexual act. Sexual desire

may change during different times in the menstrual cycle, peaking at the time of ovulation

because of higher levels of estrogen.

Local sexual stimulation of the vulva, vagina and other perineal regions and especially the

glans of the clitoris may increase sexual desire.

The sexual sensory signals are transmitted via the pudendal nerve and sacral plexus to the

spinal cord. There are also some local reflexes integrated in the sacral and lumbar spinal cord.

Question 34

Describe female erection and lubrication.

Answer 34

The clitoris contains erectile tissue similar to the penis controlled by parasympathetic

nerves. Early in the arousal phase, the parasympthetics cause dilation of the arteries of the

erectile tissue from the release of acetylcholine, nitric oxide, and vasoactive intestinal

polypeptide (VIP) at the nerve endings (Viagra works though the above pathways). This

causes engorgement of the female external genitalia so it literally tightens around the penis

(this is called the plateau phase). The majority of lubricant for sexual relations comes from

the vaginal wall and not the glands in that area (always a favorite test question).

Question 35

Describe the female orgasm.

Answer 35

Also called the female climax. The book stresses that female orgasms are very important

for fertilization…but I disagree. When we treat women with unexplained infertility,

studies show that intrauterine insemination has a higher success rate…but we will cover

that next year.

The perineal muscles of the female contract rhythmically as a result of spinal cord reflexes.

Uterine contractions are also seen. The above responses are more sympathetically

controlled.