Reproduction 2: Pregnancy and Lactation

Question 1

Prolactin is synthesized by ? and is under the control of ?

Answer 1

Prolactin is synthesized in the ant pit by LACTOTROPHS and it secretion is under the control of hypothalamus.

Question 2

What are the 2 regulatory pathways in which the hypothalamus controls the secretion of PRL?

Answer 2

1. an inhibitory pathway thru dopamine.
2. a stimulatory pathway through Thyrotropin releasing hormone [TRH]
   In persons who are not pregnant/lactating,PRL secretion by ANT PIT is TONICALLY INHIBITED BY DOPAMINE. In other words, PRL is maintained at low levels b/c inhibition of PRL secretion by dopamine overrides stimulation of PRL secretion by TRH.

Question 3

How does the inhibitory dopamine reach the lactotrophs of the ant pit?

Answer 3

Dopaminergic neurons secrete dopamine into median eminence of the hypothalamus. The hypothalamic-hypophysial portal vessels deliver dopamine directly, and in high concentration, to the lactotrophs of the ant. pit.

Question 4

Why amenorrhea with a prolactinoma?

Answer 4

PRL inhibits the secretion of GnRH which leads to decreased LH. The surge in LH initiates ovulation.

Question 5

What drugs can inhibit or lower PRL levels? And what is its mechanism of action?

Answer 5

Dopamine agonists such as Bromocriptine, inhibit PRL secretion by ant pit. Systemically, acts just like dopamine.

Question 6

Gonadotropin secretion over the life-span:

Answer 6

Begins during fetal stage. During childhood LH starts steroidal hormone synthesis by increasing activity of P450scc. During menopause,there is little neg feedback to hypothal/ant pit with few developing follicles. In older men, testosterone secretion diminishes somewhat→ less neg feedback also.

Question 7

Why must fertilization occur soon after ovulation?

Answer 7

Oocyte only lives 12-24 hrs and sperm live 2-5days. Oocyte-cumulus complex is ovulated into peritoneal space. Fimbriae of the oviduct recognize the cumulus and sweep the complex into the ampulla where ferilization takes place. Hyaluronidase enzymes on the sperm head hydrolyze the ECM around the cumulus cells to permit the sperm(with acrosome intact) to make its way to the zone pellucida.

Question 8

Before sperm can fertilize the ovum, they must undergo CAPACITATION in the female reproductive tract. What is the process and how long does it take?

Answer 8

Capacitation takes 4-6 hours and involves biochemical and structural modifications of the sperm that result in:

1. Tails develop hyperactive motility
2. Changes in membrane of the head make it capable of reaching the cell membrane of the egg and fusing with it. Fusing with the membrane involves the acrosomal reaction.

Question 9

How long do human sperm remain capacitated for?

Answer 9

1-4 hrs. In not “called into action” they lose ability to fertilize the oocyte. Not all sperm undergo capacitation at once, so a population that is no longer fxnl is replaced by a new one. (Sperm stored in oviduct go through waves of capacitation)

Question 10

How does motility develop during capacitation?

Answer 10

Cytoplasm of sperm is acidic and enters alkaline environment of vagina. Protons leave the sperm cytoplasm through Hv1 channels in the flagellum. As more protons are lost, the flagellum starts to beat in a whip like manner. The change in pH influences role of Ca2+ channels and the calcium influx-permits flagellar motion.

Question 11

Are sperm motile in the male reproductive tract?

Answer 11

NO! They become motile in the alkaline environment of the vagina and undergo capacitation and are capable of undergoing acrosomal reaction.

Question 12

What happens to the sperm in the vicinity of the egg? ECF pH is 7-8

Answer 12

Alkaline pH triggers opening of Ca channels. Influx of Ca ions contributes to increasingly whip-like tail motions. Hv1 may be used as a target for controlling male fertility.

Question 13

Only 100-1000 sperm reach the oviduct. What facilitates the sperm reaching oviduct?

Answer 13

High sperm count, must be 20x10^6.
Uterine & oviduct contractions may be stimulated by ↑estrogen, oxytocin released during intercourse, prostaglandins in semen.
Sperm dysfunction-most common cause of infetility

Question 14

How does progesterone as an attractant(chemoattractant/chemotaxis) for the sperm to find the egg?

Answer 14

Progesterone initially influences the direction of the sperm’s movement by initially binding to a sperm transmembrane receptor assoc. with adenylyl cyclase and exerting it’s effects via genomic actions.

Question 15

Which cells secrete the chemical attractant?

Answer 15

cumulus cells or gr cells. The chemical attractant secreted by the oocyte itself is unknown.

Question 16

Thermotaxis?

Answer 16

Traveling along a temperature gradient appears to be caused by increased [Ca]i mediated by PLC and IP3.

Question 17

How do the sperm cells get through the cloud of gr/cumulus cells to get to the zona pellucida in order to initiate the acrosomal reaction?

Answer 17

the sperm heads secrete hyaluronidase enzymes to get through cumulus cells to the z. pellucida. Hyaluronidase enzymes forge a path through granulosa cells.

Question 18

How do sperm cells undergo the acrosomal reaction?

Answer 18

Bind to specific sites on the z. pellucida and undergo the acrosomal reaction. The enzymes released cut a path through the z. pellucida.

Question 19

Acrosomal rxn: SNARE dependent exocytosis of proteolytic enzymes requires Ca. Since sperm do not possess ER for Ca storage, where does the Ca come from?

Answer 19

Instead Ca stores are maintained at 2 different sites.
1.Ca stored in the acrosome regulates the acrosomal rxn.
2.Ca stored in the neck or mid piece-regulate motility and hyperactivation.
Sperm also possess Ca channels, pumps, and transporters.

Question 20

What happens once fertilization occurs?

Answer 20

the oocyte completes the 2nd meiotic division and releases the 2nd polar body. The sperm and oocyte pronuclei fuse to form the zygote nucleus.

Question 21

Fusion of egg and sperm membrane triggers the CORTICAL REACTION of the oocyte. What is the cortical rxn?

Answer 21

Cortical granules in the peripheral cytoplasm release their contents into the perivitelline space. The cortical substances alter the membrane and z. pellucida to prevent more than 1 sperm from fusing with the oocyte. This accomplishes “block to polyspermy”

Question 22

The ENTIRE sperm cell enters the oocyte! What happens next?

Answer 22

the flagellum and mitochondria are degraded within the cytoplasm. The centriole becomes an organizing element of the mitotic spindle. The 2nd meiotic division which was arrested in metaphase will be completed. Upon fertilization, the zygote produces enzymes that contribute to the development of the conceptus-a ball of cells resulting from repeated mitotic divisions of the zygote. Fetilization is often referred to as conception.

Question 23

What is estriol?

Answer 23

Androgens secreted by the fetus are converted to estriol by the placenta. Its an estrogen.

Question 24

Where is estriol synthesized?

Answer 24

estriol is synthesized by steps in the placenta, fetal adrenal gland, and fetal liver.

Question 25

PRL postscript:

Answer 25

In males, may induce production of LH receptors in testes.

In both sexes, may enhance immune fxns and angiogenesis.

Question 26

Prolactin deficiency:

Answer 26

usually a problem with lactotrophs in ant pit → inability to lactate.

Question 27

Prolactin excess:

Answer 27

Caused by prolactinoma in pit or INTERRUPTION OF HYPOTHALAMIC-HYPOPHYSIAL TRACT→galactorrhea and infertility. Tx with dopamine agonist:BROMOCRIPTINE.

Question 28

Antipsychotic drug chlorpromazine (Thorazine)

Answer 28

Antagonist to dopamines receptors on prolactin cells and can cause hyperlactinemia and galactorrhea in males and females.

Question 29

Sheehan’s Syndrome

Answer 29

Infarct/necrosis of Anterior Pit caused by excessive peripartum blood loss and hypervolemia.