Hypothalamic Progesterone Essay

Question 1: State the hypothesis and explain how you came up with it based on the initial observations.

GnRH is released into the anterior pituitary gland and here it stimulates the production of follicle stimulating hormone (FSH) and lutenising hormone (LH).

GnRH binds to its receptor on gonadotrope cells, stimulating the biosynthesis and secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH travel through the peripheral circulation, acting at the gonads to stimulate gametogenesis and steroidogenesis. Gametogenesis is the development of mature eggs and sperm. steroidogenesis is the synthesis of the gonadal hormones ‒ estrogen, progesterone, and androgens. In the majority of physiologic conditions, the gonadal steroids feedback at the hypothalamus and pituitary to decrease GnRH and gonadotropin

Estrogen is the primary female sex hormone and is responsible for the development and regulation of the female reproductive system and of secondary sex characteristics. Produced primarily by the ovaries, estrogen binds to and activates estrogen receptor beta (ER)- a nuclear receptor. Estrogen plays an important role in the hypothalamic-pituitary-gonadal (HPG) axis by acting on gonadotropin-releasing hormone (GnRH) neurons located within the hypothalamus. In females, a cyclic reversal of estrogen feedback produces a positive feedback loop at both the hypothalamic and pituitary levels. This is coupled with an increase in pituitary sensitivity to GnRH, which produces the massive surge of luteinizing hormone (LH) that triggers ovulation. However, LH is not only secreted during this surge- it is secreted in a pulsatile manner otherwise. This paper will focus on the implications on LH pulsatility by knocking out ER, as well as by removing the ovaries.

Progesterone is a steroid hormone most commonly found in the female reproductive cycle. The following diagram represents three feedback loops for the menstrual cycle. The blue feedback loop shows two hormones, FSH and LH, secretion as to begin the growth of the follicle then the hormones work together to start the estrogen secretion the estrogen then has a negative feedback from FSH causing it to stop been desecrate. The red feedback loop shows, increased levels of estrogen occur midpoint in the cycle causing positive feedback to respond on the LH cells in the pituitary. As LH levels rise ovulation will occur. The purple feedback loop concludes after ovulation and shows the follicle cells transform into corpus luteum which secrets then builds up progesterone and estrogen levels forming the endometrial lining the hormones work together and a second negative feedback signal is sent to allow the release of FSH and LH. The corpus luteum then deteriorates dropping the production of estrogen and progesterone allowing menstruation to occur. https://sbi4u2013.wordpress.com/2013/03/03/the-menstrual-cycle-feedback-loop/

The point in the menstrual cycle where the FH and LSH levels are elevated is during ovulation. Ovulation begins approximately on the 14 of the menstrual cycle (Levay, Baldwin, Baldwin, 2015). According to Levay et al. (2015), ovulation is defined as the time in which the ovary releases an ovum. In particular, it is the ruptured follicle that releases that ovum. Right before ovulation, during the HPG feedback loop, the estrogen levels to go up and change the feedback from negative to positive. That causes hormones such as GnRH, LH, and FSH to be secreted. This is what triggers ovulation (Levay et al., 2015). The increase in estrogen then causes the increase in LH levels. During this time, the ovaries and uterus are experiencing many changes.

After reaching maturation, the follicle undergoes ovulation; an event stimulated by a surge in luteinising hormone release from the anterior pituitary gland (orange line). The remnant follicle (now termed the corpus luteum) secretes progesterone (red line), which maintains the endometrial lining and causes it to enter the luteal phase. With triphasic COC’s, three incremental doses (phases 1-3) of progestogen (blue line) with (pink line)/without (dashed pink line) a phase 2 dose increase in oestrogen are delivered over 21 days. This is followed by a 7-day placebo period, which induces menstruation (placebo). Exogenous delivery of hormones in this way achieves contraception with significantly lower doses of progestogen, whilst crudely mimicking endogenous increases in oestrogen and progesterone. As such, it was hypothesised that the triphasic regimen would afford various benefits over monophasic COC’s.

Leuprolide acetate is a synthetic nonapeptide and analogue of naturally occurring luteinizing hormone releasing hormone (LHRH). It possesses greater biological potency than the natural hormone, which when introduced into the systemic circulation induces the release of luteinizing (LH) and follicle stimulating hormone (FSH) from the anterior pituitary (Schally et al., 1971). It is the blood-borne messenger between the hypothalamus and the anterior pituitary, which controls reproductive function. LHRH is a decapeptide hormone (pGlu-His-Trp-Ser-Tyr-GlyLeu-Arg-Pro-Gly-NH,), which is synthesized and stored in the hypothalamus in neurons which project to the median eminence. LHRH is released in periodic bursts into the hypophyseal portal circulation, where it induces the release of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) into the systemic circulation. These factors then produce a trophic and steroidogenic effect upon the gonadal tissues (Rippel et al., 1974; Johnson et al., 1976).

Levonorgestrel inhibits secretion of GnRH, LH and FSH through negative feedback to hypothalamic-pituitary-gonadal axis. Levonorgestrel inhibits secretion of LH and FSH from anterior pituitary and these indirectly causes a delay in follicle development. Decreased level of LH also lead to delay or inhibition of LH surge, which then inhibits ovulation. According to Danielsson (2010), when LNG was administrated at two to three days before LH surge, the LH peak was inhibited or delayed. However, when LNG was provided one day before or on the day of LH surge, it failed to inhibit ovulation.

Reproductive physiology is comprised of many tightly coordinated functions of the endocrine system including the hypothalamus, pituitary and reproductive organs whose dynamic function plays several critical roles in growth and development as well was reproduction. The hypothalamic-pituitary-gonadal axis plays a critical role in the development and regulation of the reproductive system. These tightly regulated functions within the pituitary must respond to continuously changing signals from the central nervous system gonads and provide the quick responses. The hypothalamic-pituitary-gonadal axis is comprised of major hormones, including gonadotropin-releasing-hormone (GnRH), luteinizing hormone (LH) and follicular stimulating hormone (FSH) and operate through both positive and negative feedback loops in mammals.1 When toxicants affect any part of this axis’s function, either by altering cellular activity or the signals themselves, the physiology can impacted by immediate and downstream effects. An understanding of the endocrinology of male and female reproduction, is required to understand how toxicological effects can have severe consequences on reproductive physiology.

2003, pg. 23). The vertebrate hormones are secreted in response to three types of stimulus. The first stimulus can be the presence or change in concentration of a specific substance in the blood; for example an decrease in blood glucose levels triggers the secretion of glucagon hormone from the ?-cells of the islets of Langerhans in the pancreas. Another stimulus which initiates the release of a hormone, is the presence or change in concentration of another hormone in the blood such as the presence of thyroid stimulating hormone which clearly stimulates the thyroid gland to secrete the amine hormone, thyroxin. The third and final type of stimuli to cause a change in hormone action is by nervous stimulation which involves neurons of the autonomic nervous system and can be clearly illustrated in the secretion of adrenaline from the adrenal gland in

The authors of this study thoroughly analyzed the underlying neural mechanisms of supplemental hormones and how they affect participants as opposed to using a placebo. Research into human behavior as it relates to neuroendocrinology will be crucial to future generations and their interrelations.

One place where steroid binding appears to exert its effect is in the hypothalamus. The sexually dimorphic nucleus of the medial preoptic area (SDN-POA) is a sub-nucleus in the medial preoptic area that is approximately 2.5 times larger in males than in females. In addition, the presence of two sexually dimorphic cell groups has been confirmed in the preoptic-anterior hypothalamic area. There are four interstitial nuclei of the anterior hypothalamus and the two that are larger in the male brain are the INAH3 and INAH1. These hypothalamic findings are particularly noteworthy because the preoptic area has been shown to be sexually dimorphic in several other non-human species and more important, to be sensitive to prenatal or perinatal hormonal influences.

In mammals, we find that the body requires certain systems to function properly and effectively in order to grow. The endocrine system is one of the physiological systems that primarily regulates growth and plays a vital role in the onset of post-natal growth as well as the onset and cessation of pubertal growth. There are also other contributors such as nutrition and genetics, etc. that influence these growth patterns. The endocrine system is a vital messaging system that relies completely on hormone delivery to specific cells. The medium of this delivery is the blood in the venous system which means that the hormones secreted can reach target cells often located far from the endocrine glands; this is an efficient method as the endocrine system regulates activities that require duration rather than speed. This efficient system means that homeostasis can be maintained. As the hormones are distributed in the blood through the venous system, this results in the whole body being exposed to these hormones and therefore the fact that only the target cells have specific binding receptors for the particular hormone means that only those target cells will respond to the exposure of the hormone. Once the hormone is bound to its specific target cell receptors, a chain of events within the target cells occurs that brings about the hormones final effect. (Sherwood, 2016)

Las principales secreciones de la corteza suprarrenal son el cortisol, aldosterona, y los andrógenos androstenediona y dehidroepiandrostenediona (DHEA). El cortisol, regulada por el sistema hormona liberadora de corticotropina(CRH)-corticotropina(ACTH)-cortisol, es una hormona importante para el metabolismo y la respuesta fisiológica al estrés. La aldosterona, regulada por el sistema renina-angiotensina-aldosterona, es una hormona involucrada en el equilibrio hídro-electrolítico; los andrógenos participan en la fisiología de la función gonadal.